Conjugative Plasmids Disseminating CTX-M-15 among Human, Animals and the Environment in Mwanza Tanzania: A Need to Intensify One Health Approach

Abstract

Background: Globally, blaCTX-M-15 beta-lactamases are the most popular extended spectrum beta-lactamase alleles that are widely distributed due its mobilisation by mobile genetic elements in several compartments. We aimed to determine the conjugation frequencies and replicon types associated with plasmids carrying blaCTX-M-15 gene from Extended Spectrum Beta-lactamase producing isolates in order to understand the dissemination of resistance genes in different compartments. Material and methods: A total of 51 archived isolates carrying blaCTX-M-15 beta-lactamases were used as donors in this study. Antibiotic susceptibility tests were performed as previously described for both donors and transconjugants. Conjugation experiment was performed by a modified protocol of the plate mating experiment, and plasmid replicon types were screened among donor and transconjugant isolates by multiplex Polymerase Chain Reaction in a set of three primer panels. Results: The conjugation efficiency of plasmids carrying blaCTX-M-15 was 88.2% (45/51) with conjugation frequencies in the order of 10−1 to 10−9 and a 100% transfer efficiency observed among E. coli of animal origin. Majority of donors (n = 21) and transconjugants (n = 14) plasmids were typed as either Inc FIA or Inc FIB. Resistance to non-beta-lactam antibiotics was transferrable in 34/45 (75.6%) of events. Ciprofloxacin, tetracycline and sulphamethoxazole-trimethoprim resistance was co-transferred in 29/34 (85.3%) such events. Gentamicin resistance was transferred in 17/34 (50%) of events. Conclusions: Majority of plasmids carrying blaCTX-M-15 were conjugatively transferred by IncF plasmids along with non-beta lactam resistance. There is a need for more research on plasmids to understand how plasmids especially multi replicon plasmids interact and the effect of such interaction on conjugation. One Health approach is to be intensified to address antimicrobial resistance which is a public health threat.

Use of Nanopore Sequencing to Characterise the Genomic Architecture of Mobile Genetic Elements Encoding blaCTX-M-15 in Escherichia coli Causing Travellers’ Diarrhoea

“…The co-location of bla CTX-M-15 with other AMR determinants such as plasmid-mediated quinolone (PMQR) & aminoglycoside resistance genes has been previously reported ( Carattoli, 2009 ; Agyekum et al, 2016 ; Irrgang et al, 2017 ; Minja et al, 2021 ) with further correlation to narrow-spectrum ß-lactamases, sulfonamide & dihydrofolate reductase resistance genes ( Singh et al, 2018 ; Awosile and Agbaje, 2021 ). These reports are consistent with our findings that bla CTX-M-15 was associated with PMQR ( qnrS1 ), aminoglycoside ( aadA1 ), sulfonamide ( sul2 ), dihydrofolate reductase ( dfrA1 ) and other ß-lactamase resistance ( bla TEM ; Figure 4 ).…”

“…In contrast to the IncFIB plasmids described above, p786605 (IncI1 plasmid) encoded several AMR determinants ( dfrA1, aadA1, bla TEM , sul2 and qnrS1 ) in addition to bla CTX-M-15 . MDR bla CTX-M-15 -encoding plasmids have been identified in previous literature but are most commonly associated with IncFII-FIA-FIB plasmid replicons ( Awosile and Agbaje, 2021 ; Minja et al, 2021 ). Analysis also identified the intI1 gene, suggesting the presence of a class 1 (C1) integron ( Ghaly et al, 2017 ; Awosile and Agbaje, 2021 ).…”

“…Therefore, monitoring AMR in GI pathogens is essential to inform treatment guidelines. Furthermore, GI bacterial pathogens can act as a reservoir for AMR determinants in the gut of humans and animals ( Minja et al, 2021 ). The gut microbiome facilitates the transfer of AMR determinants mainly via horizontal gene transfer (HGT) due to its high density and diversity of bacterial microorganisms ( Penders et al, 2013 ).…”

Extended Spectrum β-Lactamase Producing Lactose Fermenting Bacteria Colonizing Children with Human Immunodeficiency Virus, Sickle Cell Disease and Diabetes Mellitus in Mwanza City, Tanzania: A Cross-Sectional Study

“…The bla CTXM has been the most frequently detected ESBL allele among ESBL-LF in our setting and other settings [ 23 , 33 ]. The predominance of the bla CTXM gene may be due to the fact that these genes are encoded by conjugative epidemic plasmids, i.e., IncFII, which play an important role in the effective spreading of this allele [ 34 ]; these plasmids have been commonly detected in this setting [ 35 ].…”

Occurrence of EBSL and quinolone resistance genes among Escherichia coli and Klebsiella pneumoniae isolated from poultry, domestic pigs and environment in the Msimbazi River Basin in Tanzania

“…The high level of antimicrobial use (AMU) and antimicrobial resistance (AMR) poses a threat to public and animal health given the fact that they are associated with development and spread of antimicrobial resistance genes, which can be transferred across animal, human and environment compartments as shown in a previous study [12][13][14][15][16]. Indeed, conjugative plasmids have been responsible for disseminating CTX-M-15 among human, animals and the environment [13].…”