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Molecular Detection and High-Frequency Horizontal Gene Transfer of ESBL Genotype from Proteus Species to Escherichia coli: Implications for the Spread of WHO Priority Pathogens in North-Eastern Nigeria

Tom, I. M.; Ali, H. B.; Ibrahim, A. A.; Dutsinma, U. A.; Ibrahim, M. M.; Umoru, A. M.; Balla, H. J.

2026-04-30 epidemiology
10.64898/2026.04.29.26352026 medRxiv
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BackgroundThe rise of antimicrobial resistance (AMR) in the Lake Chad Basin poses a significant threat to global health. While Escherichia coli and Klebsiella pneumoniae are primary concerns for the WHO, Proteus species have emerged as important clinical pathogens and potential reservoirs for genetic resistance. This study aimed to analyze the molecular diversity and horizontal gene transfer (HGT) potential of ESBL-producing Proteus species in the region. MethodsA regional surveillance was conducted with 1,500 clinical samples from Borno, Adamawa, Bauchi, Gombe, Taraba, and Yobe states. Proteus isolates were identified biochemically, and antibiotic susceptibility was assessed using the Kirby-Bauer method. Resistance genes (blaTEM, blaSHV, blaCTX-M) were identified via PCR, and HGT was evaluated through conjugation assays. ResultsA total of 144 Proteus isolates were identified, with a prevalence of 9.6%. P. mirabilis was the dominant species (90.97%). Phenotypic screening indicated that 69.44% produced extended-spectrum beta-lactamases (ESBL), with high resistance rates observed for Cefotaxime (80.56%) and Ampicillin (84.72%). Alarmingly, resistance to Ertapenem reached 54.86%. Molecular analysis showed blaTEM as the predominant gene (81.69%), and the conjugation assay revealed a high HGT rate of 76.92%, confirming blaTEM acquisition by E. coli. ConclusionThese results indicate that Proteus species in North-Eastern Nigeria are significant reservoirs for genetic resistance, facilitating the spread of ESBL markers. The high frequency of HGT raises concerns about the effectiveness of beta-lactam therapies in sub-Saharan Africa, underscoring the need to include Proteus in the GLASS framework and promote regional antimicrobial stewardship efforts. Current UnderstandingAntimicrobial resistance (AMR) in Enterobacteriaceae, particularly with Escherichia coli and Klebsiella pneumoniae, is a significant global issue highlighted by the World Health Organizations Global Antimicrobial Resistance and Use Surveillance System (WHO GLASS). While Proteus species are recognized as opportunistic pathogens, their role as genetic reservoirs in sub-Saharan Africa, especially in the Lake Chad Basin, remains inadequately defined in surveillance data. Study ContributionThis study identifies Proteus species as a critical "Genetic Hub" for the transmission of extended-spectrum beta-lactamases (ESBL) in North-Eastern Nigeria, revealing a high horizontal gene transfer (HGT) rate of 76.92% for the blaTEM genotype to E. coli. It also shows a concerning 54.86% resistance rate to Ertapenem, underscoring the urgent need to include Proteus in regional stewardship and global surveillance efforts.

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