Multi-Drug Resistant Genes in Bacteria and 21st Century Problems Associated with Antibiotic Therapy

Author(s): Asit Kumar Chakraborty

Bacterial infections are cured by antibiotics since 1930s but recently such antibiotics would not work to cure most bacterial infections due to accumulation of many MDR genes in bacterial plasmids. Most notorious MDR gene is β-lactamase gene (bla) which hydrolyses lactam ring CO–N bond of penicillin. Other MDR genes include tet gene isomers which encode a membrane-bound drug efflux protein (~400 aa) which kicks out tetracycline from bacterial cell cytoplasm. strA/B gene encodes an enzyme (~267 aa) that phosphorylates streptomycin and phosphorylated streptomycin could not bind bacterial 50S ribosome. Similarly, diversified aad and aph MDR genes adenylate and phosphorylate aminoglycoside antibiotics which then could not able to bind ribosome to kill bacteria. cat gene acetylates chloramphenicol and acetylated chloramphenicol could not bind 30S ribosome Diversified aminoglycoside acetyl transferases (aacA1 and aacC1) also acetylate at various position of neomycin, amakacin and gentamycin. arr gene ribosylates refamycins which then could not inhibit bacterial RNA polymerase. Sul1/2 genes have been implicated in sulfamethoxazole resistant in the recent outbreaks of Stenotrophomonas maltophilia. VanA gene cluster are involved in the vancomycin resistance in Enterococcus facium as well as Staphyloocucus aureus and recently in Escherichia coli. ermA/B genes are diverged 23S rRNA methyl transferases that give resistant to macrolides. Other potential genes are MFS, RND and MATE types drug efflux genes that could kick out drugs in a proton-pump mechanism. Similarly, certain drug ABC transporters efflux antibiotics like doxorubicin with ATPase activity and mcr-1 gene (phosphoethanolamine transferase) gives resistant to colistin drug. Thus, we see that diverse MDR genes are present in E. coli, K. pneumoniae, S. aureus, S. enterica, P. aeruginosa, and many other common pathogens both located in large conjugative plasmids and chromosome. The author concluded that golden era of antibiotic had ended within 80 years of its discovery and alternative medicines like heterogeneous herbal antibiotics, bacteriophage therapy and gene medicines (antisense, ribozyme and miRNA) were now popular all over the world.

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