Correspondence

Dissemination of the mcr-1 colistin resistance gene

Global emergence of multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium is a continuing challenge for modern healthcare. However, the knowledge, regarding the epidemiology of salmonellosis caused by the monophasic variant S. 4,[5],12:i:- in hospitalized patients, is limited in China. To bridge this gap, we carried out a retrospective study to determine the antimicrobial resistance, trends, and risk factors of S. Typhimurium and S. 4,[5],12:i:- (n = 329) recovered from patients in Zhejiang province between 2011 and 2019. The results showed that 90.57% (298/329) of the isolates were MDR; among them, 48.94% (161/329) and 12.46% (41/329) were phenotypically resistant to cephalosporins and fluoroquinolones, respectively, which are the drugs of choice used to treat salmonellosis in clinics. Additionally, we observed a higher incidence of infections among the young population (<5 years old). Notably, the higher prevalence of ST34 (sequence type 34) isolates, especially after 2014, with MDR (57.05%, 170/298) phenotype, and incidence of ST34 isolates co-harbouring mcr-1 (mobile colistin resistance gene) and bla_CTX-M-14 (β-lactamase gene) suggest an association between STs and drug resistance. Together, the increasing prevalence of MDR ST34 calls for enhanced monitoring strategies to mitigate the spread and dissemination of MDR clones of S. Typhimurium and S. 4,[5],12:i-. Our study provides improved knowledge about non-typhoid Salmonella (NTS) infections, which could help in the effective recommendation of antimicrobials in hospitalized patients.

Escherichia coli is one of the major pathogens causing mastitis in lactating mammals. We hypothesized that E. coli from the gut and mammary glands may have similar genomic characteristics in the causation of mastitis. To test this hypothesis, we used whole genome sequencing to analyze two multidrug resistant E. coli strains isolated from mammary tissue (G2M6U) and fecal sample (G6M1F) of experimentally induced mastitis mice. Both strains showed resistance to multiple (>7) antibiotics such as oxacillin, aztreonam, nalidixic acid, streptomycin, gentamicin, cefoxitin, ampicillin, tetracycline, azithromycin and nitrofurantoin. The genome of E. coli G2M6U had 59 antimicrobial resistance genes (ARGs) and 159 virulence factor genes (VFGs), while the E. coli G6M1F genome possessed 77 ARGs and 178 VFGs. Both strains were found to be genetically related to many E. coli strains causing mastitis and enteric diseases originating from different hosts and regions. The G6M1F had several unique ARGs (e.g., QnrS1, sul2, tetA, tetR, emrK, blaTEM-1/105, and aph(6)-Id, aph(3″)-Ib) conferring resistance to certain antibiotics, whereas G2M6U had a unique heat-stable enterotoxin gene (astA) and 7192 single nucleotide polymorphisms. Furthermore, there were 43 and 111 unique genes identified in G2M6U and G6M1F genomes, respectively. These results indicate distinct differences in the genomic characteristics of E. coli strain G2M6U and G6M1F that might have important implications in the pathophysiology of mammalian mastitis, and treatment strategies for mastitis in dairy animals.

Colistin is an antibiotic of last resort for treating Gram-negative bacterial infections, but resistance is spreading rapidly. In a recent issue of Nature, Wang et al. use genome mining to identify and synthesize a natural variant that bypasses colistin resistance and offers new hope for tackling antimicrobial resistance.

Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli) have been reported in wildlife worldwide. Whether wildlife is a transient host of ESBL-E. coli or comprises an independently maintained reservoir is unknown. We investigated this question by longitudinally monitoring ESBL-E. coli in common vampire bats and nearby livestock in Peru. Among 388 bats from five vampire bat colonies collected over three years, ESBL-E. coli were detected at a low prevalence (10% in 2015, 4% in 2017 and 2018) compared to a high prevalence (48%) from 134 livestock sampled in 2017. All ESBL-E. coli were multidrug-resistant, and whole genome sequencing of 33 randomly selected ESBL-E. coli isolates (18 recovered from bats) detected 46 genes conferring resistance to antibiotics including third-generation cephalosporins (e.g., bla_CTX-M-55, bla_CTX-M-15, bla_CTX-M-65, bla_CTX-M-3, bla_CTX-M-14), aminoglycosides, fluoroquinolones, and colistin (mcr-1). The mcr-1 gene is reported for the first time on a wild bat in Latin America. ESBL-E. coli also carried 31 plasmid replicon types and 16 virulence genes. Twenty-three E. coli sequence types (STs) were detected, including STs involved in clinical infections worldwide (e.g., ST 167, ST 117, ST 10, ST 156 and ST 648). ESBL-E. coli with identical cgMLST (ST 167) were detected in the same bat roost in 2015 and 2017, and several ESBL-E. coli from different bat roosts clustered together in the cgMLST reconstruction, suggesting long-term maintenance of ESBL-E. coli within bats. Most antibiotic resistance and virulence genes were detected in E. coli from both host populations, while ESBL-E. coli ST 744 was found in a bat and a pig from the same locality, suggesting possible cross-species exchanges of genetic material and/or bacteria between bats and livestock. This study suggests that wild mammals can maintain multidrug-resistant bacteria and share them with livestock.

Colistin drug resistance is an emerging public health threat worldwide. The adaptability, existence and spread of colistin drug resistance in multiple reservoirs and ecological environmental settings is significantly increasing the rate of occurrence of multidrug resistant (MDR) bacteria such as Escherichia coli (E. coli). Here, we summarized the reports regarding molecular and biological characterization of mobile colistin resistance gene (mcr)-positive E. coli (MCRPEC), originating from diverse reservoirs, including but not limited to humans, environment, waste water treatment plants, wild, pets, and food producing animals. The MCRPEC revealed the abundance of clinically important resistance genes, which are responsible for MDR profile. A number of plasmid replicon types such as IncI2, IncX4, IncP, IncX, and IncFII with a predominance of IncI2 were facilitating the spread of colistin resistance. This study concludes the distribution of multiple sequence types of E. coli carrying mcr gene variants, which are possible threat to “One Health” perspective. In addition, we have briefly explained the newly known mechanisms of colistin resistance i.e. plasmid-encoded resistance determinant as well as presented the chromosomally-encoded resistance mechanisms. The transposition of ISApl1 into the chromosome and existence of intact Tn6330 are important for transmission and stability for mcr gene. Further, genetic environment of co-localized mcr gene with carbapenem-resistance or extended-spectrum β-lactamases genes has also been elaborated, which is limiting human beings to choose last resort antibiotics. Finally, environmental health and safety control measures along with spread mechanisms of mcr genes are discussed to avoid further propagation and environmental hazards of colistin resistance.