Search

Resistance to last resort drugs such as carbapenem and colistin is a serious global health threat. This study investigated carbapenem and colistin resistance in 583 non-duplicate Enterobacteriaceae isolates utilizing phenotypic methods and whole genome sequencing (WGS). Of the 583 isolates recovered from humans, animals and the environment in Nigeria, 18.9% (110/583) were resistant to at least one carbapenem (meropenem, ertapenem, and imipenem) and 9.1% (53/583) exhibited concurrent carbapenem-colistin resistance. The minimum inhibitory concentrations of carbapenem and colistin were 2–32 μg/mL and 8 to >64 μg/mL, respectively. No carbapenem resistant isolates produced carbapenemase nor harbored any known carbapenemase producing genes. WGS supported that concurrent carbapenem-colistin resistance was mediated by novel and previously described alterations in chromosomal efflux regulatory genes, particularly mgrB (M1V) ompC (M1_V24del) ompK37 (I70M, I128M) ramR (M1V), and marR (M1V). In addition, alterations/mutations were detected in the etpA, arnT, ccrB, pmrB in colistin resistant bacteria and ompK36 in carbapenem resistant bacteria. The bacterial isolates were distributed into 37 sequence types and characterized by the presence of internationally recognized high-risk clones. The results indicate that humans and animals in Nigeria may serve as reservoirs and vehicles for the global spread of the isolates. Further studies on antimicrobial resistance in African countries are warranted.

Colistin is a last resort drug used to treat infections caused by multidrug resistant Gram-negative bacteria that have developed resistance to carbapenem. The emergence and rapid dissemination of the nine plasmid-mediated mobile colistin resistance genes (mcr-1 to mcr-9) has led to fear of pan-drug resistant infections occurring worldwide. To date, there is only limited information on colistin resistance in African countries where the drug is widely used in agriculture. In this study from Nigeria, 583 non-duplicate bacterial strains were isolated from 1,119 samples collected from humans, camels, cattle, dogs, pigs and poultry by the use of colistin-supplemented MacConkey agar, and 17.0% of the isolates (99/583) were colistin resistant. PCRs (mcr-1 to mcr-9) and whole genome sequencing (WGS) identified mcr in 21.2% of the colistin-resistant isolates: mcr-1.1 (n=13), mcr-8.1 (n=5), both mcr-1.1 and mcr-8.1 (n=2), and mcr-1.1 and mcr-5 (n=1). Nine of the 21 mcr-positive strains were isolated from human samples, with eight being K. pneumoniae, and six of these human K. pneumoniae had a high colistin MIC of >64 µg/ml. In contrast, nine of the 12 mcr-positive animal isolates were E. coli of which only two had a colistin MIC of >64 µg/ml. Our study is the first to report mcr-1 in Alcaligenes faecalis, and emergence of mcr-5 and mcr-8 in Nigeria. WGS determined that mcr-1 was localized on IncX4 plasmid, and 95.2% of mcr-1 harboring isolates (20/21) transferred colistin resistance successfully in conjugation assay. Our findings highlight the global spread of colistin resistance, and emphasize the urgent need for coordinated global action to combat resistant bacteria.