An Overview of Multi-Antibiotic Resistance in Pathogenic Bacteria - From Selected Genetic and Evolutionary Aspects - A Review

Abstract

The challenge posed by multi-drug resistance (MDR) of pathogenic organisms, spectacularly manifested in the 6 “ESKAPE” bacterium (two Gram-positive, four Gram-negative) species, should invoke new comprehensive strategies, and needs cooperation of scientists with medical, veterinary and natural science background. This review is aimed at informing newcomers, coming from the field of biology and genetics, about problems related to rapidly emerging, new multi-drug resistant, pathogenic, bacteria. Unlike persistence, the antibiotic resistance is inherited. A functioning “resistance gene” makes a susceptible organism resistant to a given antibiotic, encoding for polypeptides capable of acting either as decomposing enzymes, or acting as trans-membrane pumps, or membrane structure components capable of modifying the permeability implementing a «by pass» mechanism enabling the antibiotic molecule to reach its cellular target(s). A functioning “sensitivity gene” encode for a polypeptide, capable (directly or indirectly) of transferring toxic molecules into target cells, or of metabolizing non-transferable to transferable, or non-toxic molecules to toxic derivatives. A gene of a normal function could act as a “sensitivity” gene in the presence of antibiotics of chemical structures similar to the natural substrate of the gene product, (enzyme or binding/ trans-membrane protein). The Agrocin 84 story is a good example. Multi-drug resistance is a phenotypic consequence of the sequential accumulation of mutations, and/or up-take of plasmids or genomic islands carrying resistance genes from the environment via horizontal gene transfer, mediated by conjugative plasmid or bacteriophage carrying mobile genetic elements. Both multi-drug resistance and collateral sensitivity are evolutionary products. Some revealed evolutionary process and their Lamarckian and Darwinian interpretations are discussed. Toolkits of comparative full-genome sequencing, genomics, experimental evolution and population genetics may provide perspectives for overcoming the invincibility of multi-drug panresistance. The status of some recently emerging pathogenic bacterium species with zoonic features and of veterinary background is also discussed.

Multidrug Resistance (MDR) and Collateral Sensitivity in Bacteria, with Special Attention to Genetic and Evolutionary Aspects and to the Perspectives of Antimicrobial Peptides—A Review

“…Omadacycline aminomethylcycline is a semisynthetic derivative of tetracycline, and it is active against many Gram-negative bacteria and Gram-positives, including MRSA, S. aureus , S. pneumoniae , β-hemolytic streptococci, Enterococcus VRE, and Enterobacteriaceae in vitro [ 393 ] and in vivo in clinical practice [ 394 ]. Similar activity has also been found in the thermostable antimicrobial peptide discovered in Hungary in Xenorhabdus budapestensis and X. szentirmaii [ 31 , 395 , 396 , 397 , 398 , 399 ] and later identified as fabclavine [ 400 , 401 , 402 , 403 , 404 , 405 ].…”

“…The emergence of antibiotic multiresistance (MDR) in pathogenic bacteria has become alarming in the last decades [ 12 ]. MDR appeared not only in human clinical pathogens [ 13 , 14 , 15 , 16 ] but also in zoonic bacteria [ 17 , 18 ], veterinary pathogens [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ], and in plant pathogens [ 27 , 28 , 29 , 30 , 31 , 32 ]. Although application technologies are improving for plant pathogens [ 33 ], the trend has been that the use of antibiotics as plant medicines has gradually been restricted [ 34 , 35 ].…”

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“…The known resistance mechanisms to antibiotics include enzymatic decomposition, efflux pumps (Nehme and Poole, 2005), permeability defects, and modifications of target sites (Fodor et al, 2017). We suppose that an evolutionarily-built resistance system against a group of interacting antimicrobial peptides may need another mechanism, the details of which have not yet been discovered.…”

“…The number of pathogenic bacterium species of clinical, (Talbot et al,2006;Talbot, 2008;Dötsch et al, 2009;Cantas et al, 2013;Exner et al, 2017); veterinary (Gebreyes and Thakur 2005;Endimiani et al, 2011;Szmolka & Nagy, 2013;Moore et al, 2013;Davis et al, 2013;McManus et al, 2015;Rzewuska et al, 2015;Marques et al, 2016); and plant medical (Załuga et al, 2014;Li, Plésiat and Nikaido, 2015;Fodor et al, 2012;Fodor at al., 2017) aspects has dangerously been increasing. Those bacterium species which have been put in the ESKAPE (based on the initials of respective genus name) list (Rice, 2008) are: Enterococcus faecium, (Williamson et al, 1983;Sun et al, 2012;Gilmore, Lebreton, & van Schaik, W. 2013;Miller, Munita &Arias, 2014) Staphylococcus aureus, (MRSA) [41] (Tomasz, 1998;Tenover et al, 2008;Ellington et al, 2010;Shi et al, 2014); Klebsiella pneumoniae, (Schechner et al, 2008;Schwaber et al, 2011); Acinetobacter baumannii, (Vila, Martí, and Sanchez-Céspedes, 2007;Antunes, Visca and Towner 2014); Lee et al, 2017); Pseudomonas aeruginosa, (Nordman et al, 1993;Strateva and Yordanov, 2009;Hirata et al, 2002;Nehme and Poole, 2008;Mulcahy et al, 2010Mulcahy et al, , 2014Gonçalves-de-Albuquerquea, 2015;…”