1. Master in evolving
Antibiotics are extensively used worldwide for treating predominantly gram-negative bacterial infections and also for treating certain gram-positive infections. While the precise mechanism of their bactericidal action is yet to be unraveled, aminoglycosides, for example, act by binding to the RNA component of ribosomes, leading to both mistranslation and ultimate inhibition of protein synthesis. The widespread use of other major classes of antibiotics has resulted in the emergence of resistant bacteria by expediting the course of its evolution [1, 2]. The emergence of resistance to antibiotics is of special concern in the treatment of infections, particularly of systemic nature, by gram-negative organisms narrowing down the options for antibiotic alternatives. The resistance mechanisms displayed by the bacteria can be classified into the following: (a) reduced uptake, (b) increased efflux, (c) enzymatic modification of drug, and (d) drug target modification. Whereas resistance to streptomycin, the first widely used aminoglycoside, is predominantly through mutations in drug targets (mostly in the ribosomal protein rpsL and also in rRNA), resistance to other aminoglycosides appears to utilize a variety of mechanisms. The question arises, whether antibiotic action facilitates the emergence of resistant mutants. For certain other classes of antibiotics that induce the bacterial SOS response either by direct DNA damage (e.g., ciprofloxacin) or through indirect means (e.g., ampicillin), it has been shown that the action of the antibiotic itself plays a significant role in the emergence of mutations that confer resistance. One such mechanism, mistranslation due to defects in the translation apparatus, can promote hypermutagenesis in a phenomenon called translational stress-induced mutagenesis (TSM) raising the possibility that aminoglycoside exposure, by promoting mistranslation, could also elevate mutagenesis. According to the current understanding, TSM is mediated by a low-level mistranslational corruption of the replicative DNA polymerase leading to episodic hypermutagenesis. Exposure of wild-type bacterial cells to sublethal concentrations of an antibiotic increases mutagenic translesion DNA synthesis in vivo, and exposure of certain mutants also increases spontaneous mutagenesis. Exposure of wild-type
2. Master in dominating
Cystic fibrosis (CF) is an autosomal recessive genetic condition among Caucasians, with an incidence rate of 1 in 2500 live births. The morbidity and mortality associated with this disease condition are due to thickened lung secretions and subsequent creation of hypoxia and secondary infections predominantly by opportunistic pathogens. Bacteria such as
Apart from the abovementioned bacterial species in the CF microbiome, mycobacteria, in general, are widespread organisms except tuberculosis (
3. A friend or a foe?
Normally, tuberculosis is rare among CF patients, and it was found to complicate the CF disease condition. It is also interesting to know that the CF disease condition will not support growth of TB mycobacteria (
Among non-typical mycobacteria (NTM),
4. The concern
Huge genetic repertoire and mosaic genome structure of
References
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Winstanley C, O’Brien S, Brockhurst MA. Pseudomonas aeruginosa evolutionary adaptation and diversification in cystic fibrosis chronic lung infections. Trends in Microbiology. 2016; 24 (5):327-337 - 2.
Moradali MF, Ghods S, Rehm BH. Pseudomonas aeruginosa lifestyle: A paradigm for adaptation, survival, and persistence. Frontiers in Cellular and Infection Microbiology. 2017; 7 :39 - 3.
Stefani S, Campana S, Cariani L, et al. Relevance of multidrug-resistant Pseudomonas aeruginosa infections in cystic fibrosis. International Journal of Medical Microbiology. 2017; 307 (6):353-362 - 4.
Cox MJ, Allgaier M, Taylor B, et al. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS One. 2010; 5 :e11044 - 5.
Rossi GA, Morelli P, Galietta LJ, Colin AA. Airway microenvironment alterations and pathogen growth in cystic fibrosis. Pediatric Pulmonology. 2019; 54 (4):497-506 - 6.
Lobo LJ, Noone PG. Respiratory infections in patients with cystic fibrosis undergoing lung transplantation. Lancet Respiratory Medicine. 2014; 2 :73-82 - 7.
Chalermskulrat W, Sood N, Neuringer IP, Hecker TM, Chang L, Rivera MP, et al. Non-tuberculous mycobacteria in end stage cystic fibrosis: implications for lung transplantation. Thorax. 2006; 61 :507-513 - 8.
Jones AM. Which pathogens should we worry about? Paediatric Respiratory Reviews. 2019 [epub ahead of print]