Concurrent carriage of bla NDM plasmids in distinct Gram-negative bacterial species in the gut microbiota of pregnant mothers and neonates

OBJECTIVES: New Delhi metallo-β-lactamase (NDM), a broad-spectrum carbapenemase, can disseminate via plasmids and is a major global healthcare challenge. The gut acts as a niche for the exchange of such genes. This study investigates the transmission dynamics of blaNDM-bearing plasmids among co-colonized bacterial species in pregnant mothers/neonates. METHODS: Rectal isolates from mothers and neonates underwent antimicrobial susceptibility testing, detection of blaNDM variants, molecular typing and whole-genome/plasmid sequencing. Transmissibility of blaNDM was evaluated through conjugation. RESULTS: Among mothers (n = 86) and sick neonates (n = 93) analysed, 17 were colonized with multiple carbapenem-resistant species; with nine patients colonized with multiple carbapenem-resistant Enterobacterales (CREs), primarily blaNDM-harbouring Escherichia coli and Klebsiella pneumoniae. Isolates were distinct and belonged to diverse sequence types, including epidemic clones (ST11/15/101/147/167/648). blaNDM variants (blaNDM-1 > blaNDM-5 > blaNDM-7 > blaNDM-4) were found to reside on large conjugative plasmids (46-271 kb), primarily belonging to IncFIA-FIB-FII replicons in these isolates. Comparison of blaNDM-plasmid backbones in co-colonized bacteria revealed high diversity and different blaNDM variants, while the immediate genetic environment of blaNDM was very similar. The diverse blaNDM plasmids indicated an independent acquisition of blaNDM instead of its transmission among co-colonized bacteria in individuals. However, in one neonate, co-colonized species (E. coli and K. pneumoniae) possessing blaNDM-5 showed similarities in plasmid backbones indicating possible transmission of blaNDM among these co-colonized species. In addition, similar blaNDM plasmid backbones were observed between isolates from different neonates. CONCLUSIONS: The high co-colonization of blaNDM-harbouring bacteria, some epidemic clones, calls for targeted intestinal CRE screening. However, exchange of such genes was very low in the gut, indicating independent acquisition of blaNDM.