Diseases and symptoms of
Abstract
Pseudomonas aeruginosa is one of the common species responsible for an array of diseases in the respiratory tract, gastrointestinal tract, urinary tract, bones, joints and different systemic infections of normal and immunocompromised patients as well. It exhibits resistance to a wide variety of antimicrobial agents and expresses diverse molecular epidemiology to various established classes of antibiotics including β-lactams, fluoroquinolones, tetracycline and aminoglycosides. Despite the low permeability, hydrophilicity and nonspecific behavior of the outer membrane to small molecular transport, it is inadequate to explain the degree of resistance in P. aeruginosa. The resistance mechanism of P. aeruginosa against various chemical agents is due to the complex chromosomally encoded genes. Different strains ofP. aeruginosa having the inherent capacity for biofilm formation, further boosts the resistance under various environmental factors. This chapter explains pathogenicity, mode and types of resistance of P. aeruginosa, its impact on the economy and available remediation/reduction measures and treatments.
Keywords
- Pseudomonas aeruginosa
- quorum sensing
- adaptive resistance
- acquired resistance
- intrinsic resistance
- efflux system
1. Introduction
The development of resistance by the pathogenic
2. Overview of Pseudomonas aeruginosa pathogenesis
The infectious diseases caused by
Disease caused in humans | Symptoms | Adverse effects on human | References |
---|---|---|---|
Bacteremia | Fever, fatigue, chills, joint and muscle pain | Increasing bacterial population in the bloodstream | [13] |
Pneumonia, sinusitis | Fever, chills, difficulty in breathing, cough with or without sputum production | Deposition of liquids in the parts of the lungs. Swelling and inflammation of the nasal tract | [14] |
Folliculitis | Abscess production in the skin, redness of the skin, draining wounds | Inflammation of the hair follicles by bacteria | [15, 16] |
External ear canal Infection (otitis externa) | Ear pain, swelling, itching inside the ear, discharge from the ear, sometimes difficulty in hearing | Frequent showering leads to deposition of water and hence the growth of bacteria takes place at that location | [17, 18] |
Corneal inflammation (keratitis) | Redness, pain, swelling, inflammation, pus formation, impaired vision | The bacteria adhere to the lens and other parts of an eye within 24 h of its exposure by its cilia and flagella and forms the biofilm | [19, 20] |
Urinary tract infection | Burning with urination, cloudy or bloody urine, strong odor, rectal pain (in male), pelvic pain (in female) | The transfer of bacteria into the urethra | [21] |
Diabetic foot | Swelling of foot and ankle, dry cracks in the skin(around the heel), corns or calluses | Tissue damage in the foot and severe pain due to ingrown toenails | [22] |
The resistance of
SI no. | Strains of |
Showing resistance to antibiotic class | Mode of action | References |
---|---|---|---|---|
1. | PA40, PA43 | Amikacin | Multi-drug-resistance (MDR) | [24, 25] |
2. | ATCC 27853, P2284 | Ticarcillin/clavulanate | Production of β-lactamase | [26] |
3. | K385 | Chloramphenicol and norfloxacin | Overexpression of |
[27] |
4. | PA-M4 | Ciprofloxacin | Overexpression of |
[28] |
5. | OCR1 | Gentamicin | Overexpression of |
[28] |
6. | PAO4222 | Carbapenem (imipenem and meropenem) | Loss of porin channels in the outer membrane, expression of OprD and secreting carbapenem-hydrolyzing metalloenzyme | [29] |
7. | PAO4098E | Carbenicillin and tobramycin | Inactivation of aminoglycosides enzyme, ribosomal methyl group transferase enzyme | [27] |
8. | PAO1 | Tigecycline | Inhibition of |
[30] |
9. | KG3002 | Ofloxacin | Inactivation of |
[31] |
10. | KG3000 | Ciprofloxacin | Expression of |
[32] |
11. | PAO1 | Fluroquinolones | DNA gyrase topoisomerase IV activity | [33, 34] |
12. | PA1109 | Polymyxin E (colistin) | Modification in the LPS layer | [35, 36] |
13. | PA124 | Tetracyclines | Activation of |
[37] |
14. | PAO1 | Quinolones | Expression of |
[38, 39] |
15. | ATTC 27853, K1178 | Cephalosporin | Overexpression of |
[40] |
3. Pathogenicity of Pseudomonas aeruginosa
The virulence property of
The type-VI secretion system (T6SS) seen in case of
4. Resistance for antimicrobials in Pseudomonas aeruginosa
A wide group of
4.1 Enzymatic modification
The conformational modification and phosphorylation in the 3′-OH group is carried out by the APH enzyme. APH (3′) family of enzymes shows resistance against streptomycin, butirocin, amikacin, kanamycin and neomycin by encoding the genes such as
4.2 Impermeability resistance
Impermeability to various exocompounds in Gram-negative bacteria is due to lipopolysaccharide (LPS) present in the cell wall. LPS is made up of lipid A, oligosaccharide core and O antigen regions which are linked covalently [65]. The lipid A region is hydrophobic in nature and made up of a disaccharide of glucosamine which is phosphorylated and helps in the anchoring of LPS to the cell membrane. The core oligosaccharide is accumulation of sugar, ethanolamine, phosphate and amino acids and can be divided into inner and outer core. The O antigen is the outer domain of bacterial LPS made up of repeating glycan polymers and attached with the core region. It has been observed that the deletion of lipid A makes the bacteria susceptible to various classes of hydrophobic antibiotics and degradation of O side chains determine the smoothness and roughness of the LPS [66, 67]. The use of ethylenediaminetetraacetic acid (EDTA), some organic acids like lactic acid and citric acid are found to alter the impermeability of the
4.3 Through the efflux system
The drug efflux system in bacteria includes three major components i.e. outer membrane channel-forming protein (OMF), resistance nodulation division (RND) which helps in drug-protein antiport process and the membrane fusion protein that acts as a periplasmic link between above two components [69]. The
4.4 Modification in the outer membrane
The exoskeleton of the Gram-negative bacteria is present to resist against the adverse environmental conditions. Likewise, the outer membrane of
4.5 Resistance by biofilm
Bacterial communities aggregate themselves to a substratum and encapsulated in a proteinous polysaccharide of matrix evolved during adverse environmental condition such as various irradiation treatments and therapy which is known as biofilm. Mostly these polysaccharide/polymeric matrix leads to the formation of biofilms over a water surface and shows resistance and enhances their survivability against the antimicrobial agents [87, 88]. The formation of biofilm is predominantly found in case of various biomedical instruments such as catheter, implants, ventilator and dialyser used patients residing in the hospital [89]. The bacteria are found to evade from host immune response due to the formation of biofilms and helps in promoting collateral damage to the tissues. Only few antibiotic classes act as an effective bactericidal agent for the free-floating bacteria but it fails to act against the bacteria forming biofilms as the biofilms are 1000 times more invulnerable to it [90, 91]. During environmental stress conditions, the bacteria change from free-living unicellular form to the planktonic form and then to the attached biofilm structure which enables the survivability of the bacteria. The matured biofilm starts to segregate from a place and develop an immobile structure in the new surfaces for colonization [92, 93]. The chemical therapy of antibiotics was not effective as the molecules cannot penetrate into the complex biofilm matrix due to the production of cover like exopolysaccharides matrix known as glycocalyx [94, 95]. Mostly the pathovars of
4.6 Resistance by quorum sensing
The
There are four types of quorum sensing pathways discovered for the
4.7 Others
4.7.1 Adaptive resistance
The resistance which is dependent on the physical and chemical stresses, growth states and promotes the initiation of the regular processes inside the cell in the presence of antibiotics and reverts back to the primary condition in the removal of the inducers are known as adaptive resistance [103, 104]. Previous research studies manifested that the resistance is due to many factors like the use of sub-inhibitory concentration of antimicrobial agents, polyamines, heat shock, SOS response, pH imbalance and anaerobiosis condition [105, 106].
4.7.2 Acquired resistance
The acquired resistance involves the transfer of plasmids, prophages, DNA elements and transposons by means of transduction, transformation and conjugation. This horizontal transfer shows the β-lactam and aminoglycoside resistance in
4.7.3 Intrinsic resistance
The intrinsic resistance is due to the combination of the efflux system along with the β-lactamase and the low outer membrane permeability, the entry of antibiotic molecules through the outer membrane of the bacteria [8]. The increase in antibiotic concentration in the environment helps in the low permeability of the outer membrane permits the entry of larger compounds and antibiotics into the cell with the help of porin protein channels and makes the bacteria resistant this slow process helps in increased resistance of the organism [83, 118]. The intrinsic resistance is carried out by the help of multi-drug efflux systems like MexAB-OprM and MexXY-OprM operon along with the inactivation of enzyme β-lactams by hydrolysis [119, 120].
5. Impact of P seudomonas aeruginosa on the economy
The low membrane permeability, overexpression of efflux pump and deletion of porin channels are the cause behind the resistance of
The National Nosocomial Infection Surveillance System (NNIS) also conducted the study for statistical analysis of the resistance developed by the hospital strains of
Due to hospitalization for a significant period of time in the ICU [130] of a patient suffering from respiratory disorder [110], kidney disease [89] and other diseases which needs the ventilator along with the medical device installation are more prone to the infection of
6. Mitigation of resistance
The eradication of the resistance is highly necessary for the prevention followed by cure to
Cross-infection through hospital personnel gives rise to 30–40% of infection so irrespective of cost and time use of masks, cloths, gloves, antiseptics for the proper isolation can minimize the resistant developed in the pathovars [132]. It was observed that usual laboratory methods failed to detect the Antimicrobial-Drug resistance hence new testing methods, standards and guidelines implemented by various national and international clinical research groups for the early detection and control its outbreak [133]. The synergistic of two or more anti-bactericidal molecules is found to be an effective than monotherapy to overcome the resistance. The combination of polymixin with tobramycin is found to be an effective antimicrobial for inhibition in the formation of biofilms [134]. The combinational administration of tobramycin with aminoglycoside and macrolide clarithromycin shows a devastating effect against the biofilm [79]. Likewise, the integration of azithromycin with the tobramycin helped to destroy the bacterial biofilm when treated with
The use of nitric oxide (NO) was reported to trigger the downstream of signal processing in quorum sensing and hence the production of cyclic-di-GMP decreases hence the extracellular matrix of biofilm get destroyed [136]. The introduction of deoxyribonuclease (DNAse) directly into the biofilm of the bacterial colony as it digests the environmental DNA (eDNA) enzymatically. The
The medical equipment and the biomaterial use for implantation purpose are coated with silver which reduces the adherence and biofilm producing ability of the bacteria. The novel compounds like curlicides and pilicides have been reported to inhibit the role of adhesin molecules and hence reduces the formation of biofilms on the surfaces. The use of nanomaterials of graphene and zinc as the coating of biomedical implants are found to be effective against the biofilm formation [141]. In some instances, it is necessary to replace the device after prolonged use with the patient/s. The small molecular artificially engineered peptide 1018 was discovered with the anti-biofilm activity [142].
The pharmaceutical industries are working towards the development of vaccines to tackle the antimicrobial resistance and few are under clinical trials which are believed to be effective against the resistance [143, 144]. There are several vaccines such as polysaccharide-protein conjugates, LPS-O antigen, OprI and OprF membrane protein, live-attenuated, flagella and DNA vaccines are known to be invented for the control of antimicrobial resistance of
7. Concluding remarks
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