Acinetobacter baumannii is one of the opportunistic bacteria firstly related with the hospital acquired infection influencing primarily to weakening the patient in the ICU. It is sometimes transferred to the patient by transient colonization of hands of the workers of healthcare, and persistence on eco-surfaces. Acinetobacter baumannii inhalation aerosolized through endo-tracheal suctioning of the ventilated patient is widespread among ventilator-related pneumonia (VAP). It is infections mainly associated with ventilator-related pneumonia (VAP), community Acquired Pneumonia (CAP), invasive bacterial infections (IBIs) and UTI (urinary tract infection). It is one of the prominent uropathogens problematic with antibiotic resistance especially carbapenem resistant Acinetobacter baumannii (CRAB). Their colonization of urinary tract and establishment of infection may attributed mainly to set of virulence factors like: Acinetobactin-assisted iron acquisition system, Bap (biofilm-related protein), phospholipase D, Ata (Acinetobacter trimeric autotransporter), chaperone-usher type pilus (Csu), OmpA (outer membrane protein A), and Plasminogen-binding protein (CipA). The common drugs used for treatment Acinetobacter baumannii infections involve polymyxins, glycylcyclines, tetracyclines, mono-bactams, fluoroquinolones, aminoglycosides, antipseudomonal carbapenems, antipseudomonal cephalosporins, and sulbactam. The rates of MDR isolation or also comprehensively the resistant Acinetobacter baumannii are significantly increased and so the combination of two or more (colistin, tigecycline, or colistin-rifampicin combination therapy) drugs is sometimes used to treat infections of MDR-AB. As a conclusion the Acinetobacter baumannii engagement in urinary tract infections attributed mainly to their adhesins, invasins and intrinsic antibiotic resistance.
- A. baumannii
Acinetobacter baumannii is a polymorphic bacterium, rode shaped, gram negative, immobile, and aerobic. It is an opportunistic bacterium mainly related with the hospital acquired disease. It has highly incidence among immune-compromised people, especially those who have suffered from prolonged hospital stay (more than 90 days) . A. baumannii bacterium is one of the major states of the infections of hospitals that firstly affect the exhausted patients in the ICU, notwithstanding the prevalence to long-term care facilities and to regular wards is becoming larger. It is distinguished by its great determination in environments and has a specially ability for enhancing the resistance to every antibiotic .
Acinetobacter baumannii usually causes the hospital infections, mostly catheter-related bacteremia, and aspiration pneumonia, but also can cause infections of urinary tract and soft tissue. Community-acquired infections Acinetobacter species are progressively recorded. Transfer of Acinetobacter, and sub-sequent diseases are expedited by environmental persistence of the microbes, resistance to dehydration and avoiding host immunity [3, 4, 5].
The characteristics of virulence exhibited by species of Acinetobacter mainly arises from avoiding of quick removal by the innate immunological system, actively expediting a highly bacterial density which leads to the formation of receptor of lipopolysaccharide-Toll-like 4 (TLR4)-assisted sepsis. Polysaccharides of capsule are critical virulence agents that enable immune evasion, whereas LPSs lead to the septic shock . The newly increase in casualties, greatly related with the infected combat soldiers reverting from the conflict districts, and a high increasing in casualties of multidrug resistant isolates (MDRs) have increased the emerging opportunistic bacterium profile, significantly . MDR-
2. Acinetobacter spp.
Bacteria of the genus Acinetobacter are ubiquitous, free living, saprophytic organisms that can be isolated from soil, water, sewage, and a wide variety of foods. They are common components of food spoilage flora.
However, the highest levels of the drug resistance Acinetobacter baumannii were remarked in the states of Baltic particularly in Lithuania and in Southeastern and Southern Europe. In 2017, this bacterial species was involved in the general priority list of WHO for drug-resistant bacteria for a big need to the development of research, and the insistence for novel antimicrobial agents .
3. Urinary tract infections
4. Virulence factors
The interaction between cells of the host and pathogens is important in the pathogenesis of some bacteria leads to its internalization. Although proving the infections, the bacteria must be colonizing the host. The binding of pathogens to cells of the host is enhanced by different molecules expression or structures by cells of bacteria. Adhesion depends on the interferences of proteins of the host cell surface or soluble proteins with receptors. The proteins act as a bridge between cells of the host and bacteria. Adherence of microbes to cells of the host as a first step of colonization is an important virulence agent [40, 41]. Few molecular agents are needed to the virulence of A. baumannii in human. They involve excessively phospholipase D, OmpA (outer membrane protein A), Csu (chaperone usher type pilus), Bap (biofilm associated protein), acinetobactin assisted Fe acquisition system, and Ata (Acinetobacter trimeric autotransporter), . The role of each of them in virulence was listed below:
4.1 Bap (biofilm-associated protein)
In vitro, cells of A. baumannii easily form the biofilm, and the capability of nosocomial strains for forming the biofilm on the medical devices as in tissues of the host finds a critical agent in the virulence of bacteria. The cells that synthesize the biofilms are included in the polymeric conglomerate of polysaccharides and proteins. The biofilm resists immune defenses of the host, antibiotics and detergents, and antibiotic resistance to bacteria in these habitats can be increased to 1000 times [43, 44]. The biofilm finally grows by producing poly-beta (1-6) N-acetyl-glucosamine controlled by pgalocus. The extracellular matrix gives an adhesion among the cells of bacteria, allowing the synthesis of multilayer structures. Also, many surface proteins are included in the process, and show to expressively contribute to the binding of the bacterial cells to abiotic or biological surfaces. Directly, Bap (biofilm associated protein), a special cell surface protein, is included in the formation of the biofilm by Acinetobacter baumannii and plays a main role in the processes of infectious bacteria. It is involved in intercellular adhesion within the mature biofilm . Bap (Acinetobacter baumannii biofilm-related protein) is necessary to form a mature biofilm on the medically-relevant surfaces, involving polystyrene, titanium, and polypropylene, and Bap acts as the surface structure included in A. baumannii adherence to normal human neonatal keratinocytes and normal human bronchial epithelial cells. The finding Bap increases hydrophobicity of surface of the cell of bacteria . Bap is A giant protein plays a great role in the formation of biofilms and adhesion to cells of the host in A. baumannii. Most of the protein is synthesized by arrays of 80 to 110 modules featuring Ig-like (immunoglobulin-like) motifs. Bap types includes BLP1, and BLP2 which included in the formation of biofilms and assembled in dissimilar A. baumannii isolates. However, adhesion patterns and phenotypes of the biofilm of some clinical strains appear to be associated with the finding broadspectrum antibiotic resistances. Also, the arrangement of the development, and formation of the biofilms diverse like surfaces on which these bacteria persist and components of cells that contribute in the multi-step programmed process. The regulatory processes related with the synthesis of biofilms involve sensing density of the cells of bacteria, the finding various nutrients and concentrations of free cations found for the cells of bacteria. Extracellularlly, some of the signals maybe sensed by 2 component regulatory systems like Bfm RS. The transcriptional regulatory system activates expressions of usher-chaperone assembly systems accountable to produce pili, needed for the synthesis of the biofilms on the polystyrene surfaces, and cell attachment. Nevertheless, this system is not required for the formation of biofilms on abiotic surfaces when the cells are cultured in the industrial medium. Interestingly, system of Bfm RS controls the shape of the cell under certain cultural setting. Biofilm tolerance to host immune defenses, disinfectants, and antimicrobials [47, 48].
4.2 OmpA (Outer membrane protein A)
The main protein of outer membranes, (OmpA), is the most abundant surface protein. Also, it is necessary to bind A. baumannii to human alveolar epithelium, but it also plays a useful role in the enhancement of biofilms on plastics. Among the identified proteins of outer membrane in A. baumannii, AbOmpA acts as a porin, which is required for adhesion of eukaryotic cells, and participates to resistance of serum and the biofilm formation, partially. The OmpA group is proposed to have a variety of functions, involving adhesion to epithelial cells of the host, functions of biofilms, and complement resistance . Additionally, overexpression of chromosomal efflux systems was received great attention. However, the over-production of these systems confers increased MDR to antibacterial factors and induces death of cells of the host through nuclear and mitochondrial targeting [50, 51, 52]. OmpA thought to participate to the antibacteral resistance of
4.3 Phospholipase D
PL (Phospholipase) is an essential enzyme, necessary for phosphatidylcholine metabolism and was studied in a variety spectrum of microbes. About, 3 phospholipase classes (PLC, PLD, and PLA) were identified by the cleavage site. PLA analyzes the fatty acid of the glycerol backbone. When PLC cleavage, the phosphorylated head groups are released from PLD and phospholipid cleaves off just the head group. The releasing the polar head group and the releasing the phosphorylated head group can affect the constancy of membranes of the host cells. Additionally, phospholipase can interfere with cellular signaling by generating 2nd messengers such as phosphatidic acid, which can modify the immune responses of the host . It is assumed that many pathogens exploit certain enzymes for enhancement of membranes in the coordinated form, thus, these enzymes play an important role as virulent agents. An example is PLD (phospholipase D), an enzyme that hydrolyses structural phospholipids which results in PA (phosphatidic acid) production, a 2nd messenger that acts as an assistor in several cellular processes. Phospholipase as a virulence agent was implicated in many bacteria. In vivo, PLD of A. baumannii supports pathogenesis and invasion [55, 56]. The disrupting A. baumannii phospholipase D caused reducing capability of organisms to grow in the blood serum, decreased pathogenesis and decreasing epithelial cell invasion .
4.4 Csu (chaperone-usher type pilus)
The attachment of primary cell can be reasonably assisted by a pili -like structure encoded by the position of csu, which is widely spread among clinical strains. A. baumannii ability to form the biofilm largely depends on pilus, which assists formation and attachment of biofilms. In similar, csu E, is one of the members of the system of usher-chaperone. Genes clustered together in the form of opera csu, whose products form pili-like bundle structures in these bacteria. This gene has confirmed to be a meaningful agent in the formation of A. baumannii biofilm [58, 59].
4.5 Acinetobacter trimeric autotransporter (Ata)
The Ata (Acinetobacter Trimeric automatic transmission adhesive) pertains to the trimeric autotransporter adhesin super-family which is meaningful virulence agents in several gram negative pathogens. Also, the TAA (Trimeric autotransporter), called as the Vc type secretion system, is declared by several A. baumannii isolates, an opportunistic bacteria, answerable for the infections in hospitals globally. The TAA, is a modular homotrimeric virulence agent, including conserved membrane anchoring domain, the signal peptide, and complex stalk. In vivo, mechanisms of the evolutionary underlying the development of this adhesin is not clear. The Ata is an useful multi-functional virulence agent in the bacterium Acinetobacter baumannii that assists the invasion and the adhesion, participates with pathogenicity, and incites apoptosis . It was found that the Ata is acting as a multi-functional virulence agent of Acinetobacter baumannii by (1) mediating the invasion and adhesion in cells of epithelial and endothelial, (2) leading to the programmed cell death in a caspas-dependent manner, (3) leading to the secreting IL-6 and IL-8 as proinflammatory cytokines, and (4) in vivo, contributes to the virulence. These results forcefully propose that The Ata was uses as useful virulence factors for the bacterium Acinetobacter baumannii through the infections in models of insect and human .
4.6 System of Acinetobactin-assisted iron acquisition
The siderophore is highly converged iron chelators synthesized and applied using some bacteria to thrive under the iron-reducing which conditions typically encountered in hosts and the environment . A. baumannii produces up to 3 siderophores namely, baumannoferrin, fimsbactin, and acinetobactin. The producing baumannoferrin, and acinetobactin is beggarly conserved among clinical strains, whereas the producting fimsbactin is lesser common. Fimsbactins are structurally linked to acinetobactin by the finding catecholate, and phenolate oxazoline metal binding motifs. Both are derived from nonribosomal peptide synthesis lines with similar catalytic domain, identities, and orientations . The system of acetinopactin-assisted iron acquisition was the most distinctive system in Acinetobacter baumannii. Acinetobactins, catechol-hydroxamate siderophores, and non cyclic derivative of DHBA, that associated with N-hydroxyhistamine, and threonine. Acinetobactins are synthesized and used by 3 hypothetical systems encoded within the gene clusters of acinetobactin in Acinetobacter baumannii. Acinetobactins are manufactured from threonine, hydroxy histamine, and DHBA by the encoded proteins by genes in the gene cluster. The mixed kind siderophore, which constitutes of hydroxamite groups and catechols groups, shows a significant affinity of Fe. Acinetobacter baumannii that is produced acinetobactin is secreted system of the siderophore efflux the super-family of ABC .
4.7 CipA (plasminogen binding protein)
The CipA (Plasminogen-binding protein) is an external membrane protein, links to active forms of the plasmin, and plasminogen, to break down fibrinogen and encourage the spread of bacteria. Also, this CipA plasmin breaks down C3b. Nevertheless, there is no correlation among CipA plasmin levels, and complement resistance so far. Thus, the mechanism by which CipA gives the complement resistance still needs clarification. The CipA disrupts the system of alternative supplements and supports the penetration of layers of endothelium .
5. Antibiotic resistance and therapeutics options
A. baumannii remains difficult for treatment that has an important challenge to the clinician and cost to the systems of healthcare. Commonly, the used antibiotics to treat infections of Acinetobacter baumannii involve polymyxins, glycylcyclines, tetracyclines, fluoroquinolones, aminoglycosides, mono-bactams, antipseudomonal carbapenems, antipseudomonal cephalosporins, and sulbactam . Colistin was widely investigated as a mono-therapy or as a part of the combination treatment, but its application is limited because of the nephrotoxicity. Previously, infections of Acinetobacter baumannii to CNS (central nervous system) following neurosurgery were recorded and treated with relative success by tigecycline, colistin, intraventricular or/and intravenous or colistin-rifampicin combination thretment . Application of Colistin exhibits an upward tendency because of the VAP overseas and emergence of the bacterial infections of MDR . Nevertheless, none of tigecycline or polymyxins was excessively agreed for the medical uses in China. Actually, using combinations of beta-lactamase inhibitor (sulbactam/ampicillin and sulbactam/cefoperazone) or meropenem as the basis of the therapy program associated by levofloxacin or etilmicin is repeatedly used in therapies of the empiric antibiotics. Recently, broad spectrum antibiotics were greatly applied in the clinical practices, whereas the rate Acinetobacter baumannii resistance shows obvious increases [69, 70]. Significantly, the rates resistant Acinetobacter baumannii of or even comprehensively MDR isolation are increased in clinic. The studies were exhibited that the rate resistance of Acinetobacter baumannii to most the tested antibiotics is more than 50%. Thus, the combination of two or more antibiotics is sometimes used in treatment of the infections of MDR-AB [71, 72].
However, due to its widespread use, resistance of AB to carbapenem antibiotics quickly increased, in particular among isolates obtained from the ICU. In China, the incidence of resistance of carbapenem (CRAB) increased from the percentage 31% in 2005 to the percentage 66.7% in 2014. In USA, it increased from the percentage 20.6% in 2002 to the percentage 49.2% in 2008. Very few drugs are now available to treat CRAB (carbapenem resistant AB). It is hypersensitive to just a few drugs, like tigecycline and polymyxin, in vitro [73, 74, 75].
Currently, the best therapy for the infections of CRAB is illegible. In China, tigecycline based combination treatment, polymyxin based combination treatment, and sulbactam based combination treatment are devised to treat MDR Gram negative rode bacteria. Nevertheless, these devises are based on small scale retrospective researches, lacking comprehensive and systematic clinical study evidence, and no large scale clinical randomized controlled trials were achieved to assess their activity in the patient with MDR-A. baumannii. Polymyxin is not greatly applied in Mainland China because of the toxic side influences of it [76, 77]. Thus, currently, tigecycline treatment and sulbactam treatment are the major clinical therapies for CRAB. Nevertheless, several controversies surround tigecycline regimen to treat infections of A. baumannii bloodstream (BSI). The US Food and Drug Administration devised that tigecycline was autonomously related with highly risks of mortality and must just be applied in conditions where therapeutic preferences were limited. However, tigecycline exerts a suitable therapeutic influence depending to some researches, whereas many other researches recorded that tigecycline increases the mortality of patient [78, 79].
As a member of Gram negative bacteria, A. baumannii equipped with sets of resistance mechanisms including: i) structural bacterial shields (Presence of the porin channels and efflux mechanisms), ii) enzymatic inactivation of antibiotics (oxacillinase (OXA-type), metallo–beta-lactamases (MBLs), iii) alteration of the target or cellular functions due to mutations [80, 81, 82].
Due to extensive resistance to antibiotics, new strategies were proposed as alternative therapy. Antimicrobial peptides (AMPs) are one of the antimicrobial agents with high potential to produce new anti-
Pahge or bacteriophage therapy is another alternative therapy for MDRAP. Phages are specific to different bacteria, and they bind to receptors on bacterial cell walls to inject deoxyribonucleic acid into the cell and ultimately lyse the cell in the lytic phase. Lytic bacteriophage therapy may be an opportunity to combat the rapidly growing number of MDR bacteria . Lytic phage, the YMC 13/03/R2096 ABA BP (phage ΒФ-R2096), which specifically causes the lysis of CRAB strains .
As a conclusion the Acinetobacter baumannii engagement in urinary tract infections attributed mainly to their adhesins, invasins and intrinsic antibiotic resistance.
Conflict of interest
There is no ‘conflict of interest’ for this work.
Montefour, K., Frieden, J., Hurst, S., Helmich, C., Headley, D., Martin, M. and Boyle, D.A., 2008. Acinetobacter baumannii: an emerging multidrug-resistant pathogen in critical care. Critical care nurse, 28(1), pp. 15-25
Garnacho-Montero, J. and Timsit, J.F., 2019. Managing Acinetobacter baumannii infections. Current opinion in infectious diseases, 32(1), pp. 69-76
Dexter, C., Murray, G.L., Paulsen, I.T. and Peleg, A.Y., 2015. Community-acquired Acinetobacter baumannii: clinical characteristics, epidemiology and pathogenesis. Expert review of anti-infective therapy, 13(5), pp. 567-573
Zilberberg, M.D., Nathanson, B.H., Sulham, K., Fan, W. and Shorr, A.F., 2016. Multidrug resistance, inappropriate empiric therapy, and hospital mortality in Acinetobacter baumannii pneumonia and sepsis. Critical Care, 20(1), p.221
Liu, A., Du, W., Xie, J., Qiu, H. and Yang, Y., 2018. 720: Deficiency Of Cdc In Immunocompromised Mice With Acinetobacter Baumannii Pneumonia. Critical Care Medicine, 46(1), p.346
Wong, D., Nielsen, T.B., Bonomo, R.A., Pantapalangkoor, P., Luna, B. and Spellberg, B., 2017. Clinical and pathophysiological overview of Acinetobacter infections: a century of challenges. Clinical microbiology reviews, 30(1), pp.409-447
Howard, A., O’Donoghue, M., Feeney, A. and Sleator, R.D., 2012. Acinetobacter baumannii: an emerging opportunistic pathogen. Virulence, 3(3), pp.243-250
Munoz-Price, L.S. and Weinstein, R.A., 2008. Acinetobacter infection. New England Journal of Medicine, 358(12), pp.1271-1281
Peleg, A.Y., Seifert, H. and Paterson, D.L., 2008. Acinetobacter baumannii: emergence of a successful pathogen. Clinical microbiology reviews, 21(3), pp.538-582
Magill, S.S., Edwards, J.R., Bamberg, W., Beldavs, Z.G., Dumyati, G., Kainer, M.A., Lynfield, R., Maloney, M., McAllister-Hollod, L., Nadle, J. and Ray, S.M., 2014. Multistate point-prevalence survey of health care–associated infections. New England Journal of Medicine, 370(13), pp.1198-1208
Ainsworth, S., Ketter, P.M., Yu, J.J., Grimm, R.C., May, H.C., Cap, A.P., Chambers, J.P., Guentzel, M.N. and Arulanandam, B.P., 2017. Vaccination with a live attenuated Acinetobacter baumannii deficient in thioredoxin provides protection against systemic Acinetobacter infection. Vaccine, 35(26), pp.3387-3394
Robinson RK. Encyclopedia of food microbiology. Academic press; 2014 Apr 2
Al Atrouni A, Joly-Guillou ML, Hamze M, Kempf M. 2016. Reservoirs of non-baumannii Acinetobacter species. Front Microbiol 7:49
Mohanty, A., Kabi, A. and Mohanty, A.P., 2018. Acinetobacterlwoffii-Emerging pathogen causing liver abscess: A Case Report. National Journal of Integrated Research in Medicine, 9(5), pp.53-54
Niederman, M.S.; Kollef, M.H. The road forward in the management of Acinetobacter infections in ICU. Intensive Care Med. 2015, 41, 2207-2209
Garnacho-Montero, J.; Gutierrez-Pizarraya, A.; Diaz-Martin, A.; Cisneros-Herreros, J.M.; Cano, M.E.; Gato, E.; Ruiz de Alegría, C.; Fernández-Cuenca, F.; Vila, J.; Martínez-Martínez, L.; et al. Acinetobacter baumannii in critically ill patients: Molecular epidemiology, clinical features and predictors of mortality. Enferm. Infecc. Microbiol. Clin. 2016, 34, 551-558
Rello, J.; Kalwaje Eshwara, K.; Lagunes, L.; Alves, J.; Wunderic, R.G.; Conway-Morris, A.; Rojas, J.N.; Alp, E.; Zhang, Z. A global priority list of the TOp TEn resistant Microorganisms (TOTEM) study at intensive care: A prioritization exercise based on multi-criteria decision analysis. Eur. J. Clin. Microbiol. Infect. Dis. 2019, 38, 319-323
European Centre for Disease Prevention and Control. European Antibiotic Awareness Day (EAAD) Summary of the Latest Data on Antibiotic Resistance in the European Union; EARS-Net Surveillance Data 2015; ECDC: Stockholm, Sweden, 2016
Towner K. The genus acinetobacter. Prok. 2006;6:746-58
Munoz-Price LS, Weinstein RA. Acinetobacter infection. New England Journal of Medicine. 2008 Mar 20;358(12):1271-81
Jung J, Park W. Acinetobacter species as model microorganisms in environmental microbiology: current state and perspectives. Applied microbiology and biotechnology. 2015 Mar 1;99(6):2533-48
Lee K, Yong D, Jeong SH, Chong Y. Multidrug-resistant Acinetobacter spp.: increasingly problematic nosocomial pathogens. Yonsei medical journal. 2011 Nov 1;52(6):879-91
Flores-Mireles A.L., J. .N. Walker, M. Caparon, S.J. Hultgren, Urinary tract infections: epidemiology, mechanisms of infection and treatment options, Nature Rev. Microbiol. 13 (2015) 269-284
Patel, H.B., Soni, S.T., Bhagyalaxmi, A. and Patel, N.M., 2019. Causative agents of urinary tract infections and their antimicrobial susceptibility patterns at a referral center in Western India: An audit to help clinicians prevent antibiotic misuse. Journal of Family Medicine and Primary Care, 8(1), p.154
Baviskar, A.S., Khatib, K.I., Rajpal, D. and Dongare, H.C., 2019. Nosocomial infections in surgical intensive care unit: A retrospective single-center study. International Journal of Critical Illness and Injury Science, 9(1), p.16
Presterl, E., Diab-El Schahawi, M., Lusignani, L.S., Paula, H. and Reilly, J.S., 2019. Hospital Infections. In Basic Microbiology and Infection Control for Midwives (pp. 85-91). Springer, Cham
Lob SH, Hoban DJ, Sahm DF, Badal RE. Regional differences and trends in antimicrobial susceptibility of Acinetobacter baumannii. International journal of antimicrobial agents. 2016 Apr 1;47(4):317-23. Stickler DJ. Bacterial biofilms in patients with indwelling urinary catheters. Nature clinical practice urology. 2008 Nov;5(11):598-608
Di Venanzio G, Flores-Mireles AL, Calix JJ, Haurat MF, Scott NE, Palmer LD, Potter RF, Hibbing ME, Friedman L, Wang B, Dantas G. Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes. Nature communications. 2019 Jun 24;10(1):1-3
Lolans K, Rice TW, Munoz-Price LS, Quinn JP. Multicity outbreak of carbapenem-resistant Acinetobacter baumannii isolates producing the carbapenemase OXA-40. Antimicrobial agents and chemotherapy. 2006 Sep 1;50(9):2941-5
Coelho JM, Turton JF, Kaufmann ME, Glover J, Woodford N, Warner M, Palepou MF, Pike R, Pitt TL, Patel BC, Livermore DM. Occurrence of carbapenem-resistant Acinetobacter baumannii clones at multiple hospitals in London and Southeast England. Journal of clinical microbiology. 2006 Oct 1;44(10):3623-7
Siempos II, Vardakas KZ, Kyriakopoulos CE, Ntaidou TK, Falagas ME. Predictors of mortality in adult patients with ventilator-associated pneumonia: a meta-analysis. Shock. 2010 Jun 1;33(6):590-601
Luna CM, Aruj PK. Nosocomial acinetobacter pneumonia. Respirology. 2007 Nov;12(6):787-91
Doughari HJ, Ndakidemi PA, Human IS, Benade S. The ecology, biology and pathogenesis of Acinetobacter spp.: an overview. Microbes and environments. 2009:1103150282-
Scott P, Deye G, Srinivasan A, Murray C, Moran K, Hulten E, Fishbain J, Craft D, Riddell S, Lindler L, Mancuso J. An outbreak of multidrug-resistant Acinetobacter baumannii-calcoaceticus complex infection in the US military health care system associated with military operations in Iraq. Clinical Infectious Diseases. 2007 Jun 15;44(12):1577-84
Sheppard FR, Keiser P, Craft DW, Gage F, Robson M, Brown TS, Petersen K, Sincock S, Kasper M, Hawksworth J, Tadaki D. The majority of US combat casualty soft-tissue wounds are not infected or colonized upon arrival or during treatment at a continental US military medical facility. The American journal of surgery. 2010 Oct 1;200(4):489-95
Azizi O, Shahcheraghi F, Salimizand H, Modarresi F, Shakibaie MR, Mansouri S, Ramazanzadeh R, Badmasti F, Nikbin V. Molecular analysis and expression of bap gene in biofilm-forming multi-drug-resistant Acinetobacter baumannii. Reports of biochemistry & molecular biology. 2016 Oct;5(1):62
Greene C, Wu J, Rickard AH, Xi C. Evaluation of the ability of Acinetobacter baumannii to form biofilms on six different biomedical relevant surfaces. Letters in applied microbiology. 2016 Oct;63(4):233-9
Zeighami H, Valadkhani F, Shapouri R, Samadi E, Haghi F. Virulence characteristics of multidrug resistant biofilm forming Acinetobacter baumannii isolated from intensive care unit patients. BMC infectious diseases. 2019 Dec;19(1):629
Falagas ME, Vardakas KZ, Kapaskelis A, Triarides NA, Roussos NS. Tetracyclines for multidrug-resistant Acinetobacter baumannii infections. International journal of antimicrobial agents. 2015 May 1;45(5):455-60
Smani Y, McConnell MJ, Pachon J. Role of fibronectin in the adhesion of Acinetobacter baumannii to host cells. PLoS One. 2012;7(4). e33073
Vijayakumar S, Rajenderan S, Laishram S, Anandan S, Balaji V, Biswas I. Biofilm Formation and Motility Depend on the Nature of the Acinetobacter baumannii Clinical Isolates. Front Public Health. 2016;4:105
Harding CM, Tracy EN, Carruthers MD, Rather PN, Actis LA, Munson RS Jr. Acinetobacter baumannii strain M2 produces type IV pili which play a role in natural transformation and twitching motility but not surface-associated motility. MBio. 2013;4(4)
Giannouli M, Antunes LCS, Marchetti V, Triassi M, Visca P, Zarrilli R. Virulence-related traits of epidemic Acinetobacter baumannii strains belonging to the international clonal lineages I-III and to the emerging genotypes ST25 and ST78. BMC Infect Dis. 2013;13:282
Longo F, Vuotto C, Donelli G. Biofilm formation in Acinetobacter baumannii. New Microbiol. 2014;37:119-27
Fattahian, Y., Rasooli, I., Gargari, S.L.M., Rahbar, M.R., Astaneh, S.D.A. and Amani, J., 2011. Protection against Acinetobacter baumannii infection via its functional deprivation of biofilm associated protein (Bap). Microbial pathogenesis, 51(6), pp.402-406
Brossard, K.A. and Campagnari, A.A., 2012. The Acinetobacter baumannii biofilm-associated protein plays a role in adherence to human epithelial cells. Infection and immunity, 80(1), pp.228-233
Gaddy, Jennifer A., and Luis A. Actis. "Regulation of Acinetobacter baumannii biofilm formation." (2009): 273-278
Sefid, F., Rasooli, I. and Payandeh, Z., 2016. Homology modeling of a Camelid antibody fragment against a conserved region of Acinetobacter baumannii biofilm associated protein (Bap). Journal of theoretical biology, 397, pp.43-51
Schweppe DK, Harding C, Chavez JD, Wu X, Ramage E, Singh PK, Manoil C, Bruce JE. 2015. Host-microbe protein interactions during bacterial infection. Chem Biol 22:1521-1530
Richmond GE, Evans LP, Anderson MJ, Wand ME, Bonney LC, Ivens A, Chua KL, Webber MA, Sutton JM, Peterson ML, Piddock LJ. 2016. The Acinetobacter baumannii two-component system AdeRS regulates genes required for multidrug efflux, biofilm formation, and virulence in a strain-specific manner. mBio 7:e00430-16
Yoon EJ, Balloy V, Fiette L, Chignard M, Courvalin P, Grillot-Courvalin C. 2016. Contribution of the Ade resistance-nodulation-cell division-type efflux pumps to fitness and pathogenesis of Acinetobacter baumannii. mBio 7:e00697-16
Ismail, L.I.M., 2019. Studies on OmpA of Acinetobacter baumannii in Virulence and Immunity in a Cell Culture Model. CU Theses
Kwon H. I., S. Kim, M.H. Oh, S.H. Na, Y.J.Kim, Y.H. Jeon, J.C. LeeOuter membrane protein A contributes to antimicrobial resistance of Acinetobacter baumannii through the OmpA-like domain J. Antimicrob. Chemother., 72 (2017), pp. 3012-3015
Selvy PE, Lavieri RR, Lindsley CW, Brown HA. Phospholipase D: enzymology, functionality, and chemical modulation. Chem Rev. 2011;111: 6064-6119
Köhler, G.A., Brenot, A., Haas-Stapleton, E., Agabian, N., Deva, R. and Nigam, S. ( 2006)Phospholipase A(2) and phospholipase B activities in fungi. Biochim. Biophys. Acta, 1761, 1391– 1399
Stahl J, Bergmann H, Göttig S, et al. Acinetobacter baumannii virulence is mediated by the concerted action of three phospholipases D. PLoS ONE. 2015;10:e0138360
Jacobs, A.C., Hood, I., Boyd, K.L., Olson, P.D., Morrison, J.M., Carson, S., Sayood, K., Iwen, P.C., Skaar, E.P. and Dunman, P.M., 2010. Inactivation of phospholipase D diminishes Acinetobacter baumannii pathogenesis. Infection and immunity, 78(5), pp.1952-1962
Lee HW, Koh Y, Kim J, Lee JC, Lee YC, Seol SY, et al. Capacity of multidrug-resistant clinical isolates of Acinetobacter baumannii to form biofilm and adhere to epithelial cell surfaces. Clin Microbiol Infec. 2008;14:49-54
Tomaras AP, Flagler MJ, Dorsey CW, Gaddy JA, Actis LA. Characterization of a two-component regulatory system from Acinetobacter baumannii that controls biofilm formation and cellular morphology. Microbiology. 2008;154:3398-409
Rahbar, M.R., Zarei, M., Jahangiri, A., Khalili, S., Nezafat, N., Negahdaripour, M., Fattahian, Y. and Ghasemi, Y., 2019. Trimeric autotransporter adhesins in Acinetobacter baumannii, coincidental evolution at work. Infection, Genetics and Evolution
Weidensdorfer, M., Ishikawa, M., Hori, K., Linke, D., Djahanschiri, B., Iruegas, R., Ebersberger, I., Riedel-Christ, S., Enders, G., Leukert, L. and Kraiczy, P., 2019. The Acinetobacter trimeric autotransporter adhesin Ata controls key virulence traits of Acinetobacter baumannii. Virulence, 10(1), pp.68-81
Penwell, W.F. and Actis, L.A., 2019. Isolation and Characterization of the Acinetobactin and Baumannoferrin Siderophores Produced by Acinetobacter baumannii. In Acinetobacter baumannii (pp. 259-270). Humana Press, New York, NY
Bohac, T.J., Fang, L., Giblin, D.E. and Wencewicz, T.A., 2019. Fimsbactin and Acinetobactin Compete for the Periplasmic Siderophore Binding Protein BauB in Pathogenic Acinetobacter baumannii. ACS chemical biology
Penwell WF, Arivett BA, Actis LA. The Acinetobacter baumannii entA gene located outside the acinetobactin cluster is critical for siderophore production, iron acquisition and virulence. PLoS One. 2012;7:e36493
Koenigs A, Stahl J, Averhoff B, et al. CipA of Acinetobacter baumannii is a novel plasminogen binding and complement inhibitory protein. J Infect Dis. 2016;213:1388-1399
Karageorgopoulos DE, Falagas ME. Current control and treatment of multidrug-resistant Acinetobacter baumannii infections. Lancet Infect Dis. 2008;8(12):751-762
Lim, S.M.S., Sime, F.B. and Roberts, J., 2019. Multidrug-resistant Acinetobacter baumannii infections: current evidence on treatment options and role of PK/PD in dose optimization. International journal of antimicrobial agents
Mizrahi, C.J., Benenson, S., Moscovici, S., Candanedo, C., Benifla, M. and Spektor, S., 2019. Combination Treatment with Intravenous Tigecycline and Intraventricular and Intravenous Colistin in Postoperative Ventriculitis Caused by Multidrug-resistant Acinetobacter baumannii. Cureus, 11(1)
Tsioutis, C., Kritsotakis, E. I., Karageorgos, S. A., Stratakou, S., Psarologakis, C., Kokkini, S., et al. (2016). Clinical epidemiology, treatment and prognostic factors of extensively drug-resistant Acinetobacter baumanni ventilatorassociated pneumonia in critically ill patients. Int. J. Antimicrob. Agents 48, 492-497
Neonakis, I. K., Spandidos, D. A., and Petinaki, E. (2011). Confronting muhidrugresistant Acinetobacter baumanii: a review. Int. J. Antimierob. Agents 37, 102-109
Ayraud-Thévenot, S., Huart, C., Mimoz, O., Taouqi, M., Laland, C., Bousseau, A., et al. (2012). Control of multi-drug-resistant Acinetobacter baumannii outbreaks in an intensive care unit: feasibility and economic impact of rapid unit closure. J. Hosp. Infect. 82, 290-292
Kaliterna, V., and Goic-Barisic, I. (2013). The ability of biofilm formation in clinical isolates of Acinetobacter baumannii belonging to two different European clones causing outbreaks in the Split University Hospital, Croatia. J. Chemother. 25, 60-62
Garnacho MJ, Dimopoulos G, Poulakou G, et al. Task force on management and prevention of Acinetobacter baumannii infections in the ICU. Intensive Care Med. 2015;41:2057-75
Guan X, He L, Hu B, et al. Laboratory diagnosis, clinical management and infection control of the infections caused by extensively drug-resistant gram-negative bacilli: a Chinese consensus statement. Clin Microbiol Infect. 2016;22:S15-25
Hu FP, Zhu DM, Wang F, et al. Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005-2014. Clin Microbiol Infect. 2016;22:S9–S14
Wu X, Chavez JD, Schweppe DK, et al. In vivo protein interaction network analysis reveals porin-localized antibiotic inactivation in Acinetobacter baumannii strain AB5075. Nat Commun. 2016;7:13414
Aggarwal R, Dewan A. Comparison of nephrotoxicity of Colistin with Polymyxin B administered in currently recommended doses: a prospective study. Ann Clin Microbiol Antimicrob. 2018;17:15
Kadoyama K, Sakaeda T, Tamon A, et al. Adverse event profile of tigecycline: data mining of the public version of the U.S. Food and Drug Administration adverse event reporting system. Biol Pharm Bull. 2012;35:967-70
Xiao T, Yu W, Niu T, et al. A retrospective, comparative analysis of risk factors and outcomes in carbapenem-susceptible and carbapenem-nonsusceptible Klebsiella pneumoniaebloodstream infections: tigecycline significantly increases the mortality. Infect Drug Resist. 2018;11:595-606
Vrancianu CO, Gheorghe I, Czobor IB, Chifiriuc MC. Antibiotic Resistance Profiles, Molecular Mechanisms and Innovative Treatment Strategies of Acinetobacter baumannii. Microorganisms. 2020 Jun;8(6):935
Thomson JM, Bonomo RA. The threat of antibiotic resistance in Gram-negative pathogenic bacteria: β-lactams in peril!. Current opinion in microbiology. 2005 Oct 1;8(5):518-24
Liu J, Zhu F, Feng B, Zhang Z, Liu L, Wang G. Comparative efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for multiple drug-resistant and extensively drug-resistant Acinetobacter baumannii infections: a systematic review and network meta-analysis. Journal of Global Antimicrobial Resistance. 2020 Sep 2
Neshani A, Sedighian H, Mirhosseini SA, Ghazvini K, Zare H, Jahangiri A. Antimicrobial peptides as a promising treatment option against Acinetobacter baumannii infections. Microbial Pathogenesis. 2020 May 5:104238
Mwangi J, Yin Y, Wang G, Yang M, Li Y, Zhang Z, Lai R. The antimicrobial peptide ZY4 combats multidrug-resistant Pseudomonas aeruginosaand Acinetobacter baumannii infection. Proceedings of the National Academy of Sciences. 2019 Dec 26;116(52):26516-22
Peng J, Long H, Liu W, Wu Z, Wang T, Zeng Z, Guo G, Wu J. Antibacterial mechanism of peptide Cec4 against Acinetobacter baumannii. Infection and drug resistance. 2019;12:2417
LaVergne S, Hamilton T, Biswas B, Kumaraswamy M, Schooley RT, Wooten D. Phage therapy for a multidrug-resistant Acinetobacter baumannii craniectomy site infection. InOpen forum infectious diseases 2018 Apr (Vol. 5, No. 4, p. ofy064). US: Oxford University Press
Jeon J, Park JH, Yong D. Efficacy of bacteriophage treatment against carbapenem-resistant Acinetobacter baumannii in Galleria mellonella larvae and a mouse model of acute pneumonia. BMC microbiology. 2019 Dec 1;19(1):70