Genetic Features Influencing the Dissemination of Multidrug-Resistant Clones of Pathogenic Bacteria

Resistance to antibiotics poses a serious risk for the treatment of patients with bacterial infections resulting in considerable excess mortality. The elucidation of mechanisms permitting the acquisition and preservation of resistance determinants remains one of the highest priorities of modern medical science. The acquisition of a multidrug-resistant (MDR) phenotype is associated with the acquisition of an excess gene cargo and the emergence of a variety of changes in the host genome. It is well-established that this process encumbers the MDR bacteria with considerable fitness cost. Accordingly, bacteria evolving antibiotic resistance need extra energy to properly manage the expanded/altered genetic architecture. The enhancement of metabolic activity would ostensibly constitute a straightforward response and could, in theory, easily cover the required extra energy. However, the enhancement of metabolic activity implies that the uptake of not only nutrients but also antibiotics will be substantial. Moreover, the bacteria will have to cope with the detrimental effects of a major antibiotic-induced metabolic stress. Although bacteria can opt for a stressful response against antibiotic challenge, this type of reaction is usually transient and primarily occurs when bacteria are exposed to the grave hazard of elevated concentrations of bactericidal agents. There are limits to this “high-energy” protective response, and it is unambiguously established that, finally, when bacteria have to acquire a genuine MDR phenotype, they will always downgrade their metabolic activity, limit the uptake of antibiotics, and move toward the adoption of a highly defensive biofilm/persister form of existence.In consequence, if bacteria subsisting in an antibiotic environment are unable to obtain extra energy from enhanced conventional metabolic activity, they will have to employ/evolve devices which confer/save energy by other means. Interestingly, the acquisition of an MDR phenotype in bacteria remains the capacity of a restricted realm of species. Moreover, the spread of the highest-risk MDR pathogens — E. coli, Klebsiella pneumoniae, Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Acinetobacter baumannii, and Clostridioides difficile — is well-established to be mostly clonal. Accordingly, a few species and, in particular, some well-defined genetically related groups of those species, should command some unique “fitness traits” which permit/facilitate their dissemination in an antibiotic environment.Several fitness elements/devices facilitating a pathogen’s or clone’s capacity to cover or mitigate the fitness cost imposed by excess resistance determinants have already been identified: - a large bacterial genome is capable of accommodating excess genetic material with a small fitness cost- beneficial compensatory mutations and promotion of host codon usage (transfer of genes from plasmid to chromosome) can mitigate fitness cost conferred by plasmids- weak/tailored promoters in integron cassettes and judicious control of integrase activity save energy- the acquisition of small genomic islands and transposons salvage fitness relative to greater elements- some beneficial gyrase and topoisomerase IV mutations confer fitness gainAny new information on these elements in a clonal context would be welcome. Moreover, data on additional possible fitness-saving devices associated with MDR bacterial clones would be appreciated, for example:- economic capsule modification to resist infection with phages - judicious cell wall/porin regulation by small regulatory RNAsFurthermore, data on virulence/colonization factors obtained in a clonal setting and analyzed against a fitness background would be of interest.Moreover, since colonization with resistant bacteria often results in infection, any information on the elements mentioned above in the context of clonal colonization would be highly relevant.In this Research Topic we welcome the following article types: FAIR² DATA Direct Submission, FAIR² Data, Hypothesis and Theory, Methods, Mini Review, Opinion, Original Research, Perspective, Review, Systematic Review, Technology and Code.Contributions to this collection will advance the understanding of the complex web of determinants governing the dissemination of MDR bacteria. Topic editors: Miklos Fuzi, Salome N. Seiffert, Jun Sung Hong Source: https://www.frontiersin.org/research-topics/86010/genetic-features-influencing-the-dissemination-of-multidrug-resistant-clones-of-pathogenic-bacteria