The Co-occurrence of NDM-5, MCR-1, and FosA3-Encoding Plasmids Contributed to the Generation of Extensively Drug-Resistant Klebsiella pneumoniae

The rise and global dissemination of extensively drug-resistant (XDR) bacteria are often related to plasmid-borne mobile antimicrobial resistance genes. Notably, isolates having multiple plasmids are often highly resistant to almost all the antibiotics available. In this study, we characterized an extensively drug-resistant Klebsiella pneumoniae 1678, which exhibited high-level resistance to almost all the available antibiotics. Through whole-genome sequencing (WGS), more than 20 resistant elements and 5 resistant plasmids were observed. Notably, the tigecycline resistance of K. pneumoniae 1678 was not related to the plasmid-borne tetA gene but associated with the overexpression of AcrAB and OqxAB efflux pumps, according to the susceptibility results of tetA-transformant and the related mRNA quantification of RND efflux pumps. Except for tigecycline resistance, three plasmids, mediating resistance to colistin, Fosfomycin, and ceftazidime–avibactam, respectively, were focused. Detailed comparative genetic analysis showed that all these plasmids belonged to dominated epidemic plasmids, and harbored completed conjugation systems. Results of conjugation assay indicated that these three plasmids not only could transfer to E. coli J53 with high conjugation frequencies, respectively, but also could co-transfer to E. coli J53 effectively, which was additionally confirmed by the S1-PFGE plasmids profile. Moreover, multiple insertion sequences (IS) and transposons (Tn) were also found surrounding the vital resistant genes, which may form several novel mechanisms involved in the resistant determinants’ mobilization. Overall, we characterized and reported the uncommon co-existence and co-transferring of FosA3-, NDM-5, and MCR-1-encoding plasmids in a K. pneumoniae isolate, which may increase the risk of spread of these resistant phenotypes and needing great concern.

Characterization of a Novel Plasmid in Serratia marcescens Harboring blaGES-5 Isolated from a Nosocomial Outbreak in Japan

Serratia marcescens is a nosocomial pathogen with carbapenem resistance, limiting the availability of effective treatment options. In this study, we performed molecular characterization of GES-5 carbapenemase-producing S. marcescens isolated from an outbreak in Japan. Comparative genetic analysis revealed that the blaGES-5–encoding plasmid p2020-O-9 is a unique plasmid contributing towards carbapenem resistance. Furthermore, this study highlights the necessity of surveillance programs for monitoring novel, along with commonly occurring carbapenemases in clinical settings.

Evolution of HLA-F and its orthologues in primate species: a complex tale of conservation, diversification and inactivation

HLA-F represents one of the nonclassical MHC class I molecules in humans. Its main characteristics involve low levels of polymorphism in combination with a restricted tissue distribution. This signals that the gene product executes a specialised function, which, however, is still poorly understood. Relatively little is known about the evolutionary equivalents of this gene in nonhuman primates, especially with regard to population data. Here we report a comparative genetic analysis of the orthologous genes of HLA-F in various great ape, Old World monkey (OWM), and New World monkey (NWM) species. HLA-F-related transcripts were found in all subjects studied. Low levels of polymorphism were encountered, although the length of the predicted gene products may vary. In most species, one or two transcripts were discovered, indicating the presence of only one active F-like gene per chromosome. An exception was provided by a New World monkey species, namely, the common marmoset. In this species, the gene has been subject to duplication, giving rise to up to six F-like transcripts per animal. In humans, great apes, and OWM, and probably the majority of the NWM species, the evolutionary equivalents of the HLA-F gene experienced purifying selection. In the marmoset, however, the gene was initially duplicated, but the expansion was subjected afterwards to various mechanisms of genetic inactivation, as evidenced by the presence of pseudogenes and an array of genetic artefacts in a section of the transcripts.

Genetic evidence of widespread variation in ethanol metabolism among mammals: revisiting the ‘myth' of natural intoxication

Humans have a long evolutionary relationship with ethanol, pre-dating anthropogenic sources, and possess unusually efficient ethanol metabolism, through a mutation that evolved in our last common ancestor with African great apes. Increased exposure to dietary ethanol through fermenting fruits and nectars is hypothesized to have selected for this in our lineage. Yet, other mammals have frugivorous and nectarivorous diets, raising the possibility of natural ethanol exposure and adaptation in other taxa. We conduct a comparative genetic analysis of alcohol dehydrogenase class IV (ADH IV) across mammals to provide insight into their evolutionary history with ethanol. We find genetic variation and multiple pseudogenization events in ADH IV, indicating the ability to metabolize ethanol is variable. We suggest that ADH enzymes are evolutionarily plastic and show promise for revealing dietary adaptation. We further highlight the derived condition of humans and draw attention to problems with modelling the physiological responses of other mammals on them, a practice that has led to potentially erroneous conclusions about the likelihood of natural intoxication in wild animals. It is a fallacy to assume that other animals share our metabolic adaptations, rather than taking into consideration each species' unique physiology.