Carriage and within-host diversity of mcr-1.1- harbouring Escherichia coli from pregnant mothers: inter- and intra-mother transmission dynamics of mcr-1.1

Abstract

Exchange of antimicrobial resistance genes via mobile genetic elements occur in the gut which can be transferred from mother to neonate during birth. This study is the first to analyse transmissible colistin resistance gene, mcr, in pregnant mothers and neonates. Samples were collected from pregnant mothers (rectal) and septicaemic neonates (rectal and blood) and analysed for the presence of mcr, its transmissibility, genome diversity, and exchange of mcr between isolates within an individual and across different individuals (not necessarily mother-baby pairs). mcr-1.1 was detected in rectal samples of pregnant mothers (n = 10, 0.9%), but not in neonates. All mcr-positive mothers gave birth to healthy neonates from whom rectal specimen were not collected. Hence, the transmission of mcr between these mother-neonate pairs could not be studied. mcr-1.1 was noted only in Escherichia coli (phylogroup A & B1), and carried few resistance and virulence genes. Isolates belonged to diverse sequence types (n = 11) with two novel STs (ST12452, ST12455). mcr-1.1 was borne on conjugative IncHI2 bracketed between ISApl1 on Tn6630, and the plasmids exhibited similarities in sequences across the study isolates. Phylogenetic comparison showed that study isolates were related to mcr-positive isolates of animal origin from Southeast Asian countries. Spread of mcr-1.1 within this study occurred either via similar mcr-positive clones or similar mcr-bearing plasmids in mothers. Though this study could not build evidence for mother-baby transmission but the presence of such genes in the maternal specimen may enhance the chances of transmission to neonates.

Keywords: Colistin-resistant Escherichia coli; Illumina & MinION nanopore sequencing; mcr-1.1-bearing IncHI2; pregnant mother and neonatal gut carriage; transmission dynamics of mcr-1.1.

Figure 1.

Schematic flow diagram of the study plan, summarizing sampling/laboratory/sequencing workflows.

Figure 2.

Molecular typing and plasmid replicons of mcr-1.1 bearing Escherichia coli. Abbreviation: Indian maternal rectal sample (IN-MR), resistant (R), sequence type (ST), incompatibility (Inc), kilobase (kb), plasmid 1 (P1), plasmid 2 (P2).

Figure 3.

Alignment of mcr-1.1-bearing IncHI2 plasmid sequences of the study isolates. (a) ∼216 kb: IN-MR750R1 and IN-MR750R4 were identical, hence in this figure only IN-MR750R1 has been included. (b) ∼240 kb: Due to poor assembly issue, IN-MR364R1 was excluded from this analysis. Yellow ochre-coloured arrows: different genes, green arrow: mcr-1.1. Shaded regions: percentage similarities.

Figure 4.

Genetic environment of mcr-1.1 found among study isolates. Genes and their corresponding transcription orientations are indicated by horizontal arrows. Grey shaded region: homology, light yellow shaded region: inversion.

Figure 5.

Transmission events of mcr-1.1 gene occurring in different maternal samples. Abbreviation: India-Maternal rectal specimen (IN-MR), resistant (R), susceptible (S), not found (NF), incompatibility (Inc).

Figure 6.

A core genome phylogenetic tree summarizing the isolates with short-read WGS available from this study. Due to contamination and poor assembly issue, IN-MR364R1 and IN-MR683R1 were excluded from this analysis.

Figure 7.

Core genome phylogenetic tree of mcr-1-E. coli collected from published studies in Southeast Asia including those from the present study. Sequence type (ST), green shading: study isolates. IN-MR364R1 and IN-MR683R1 were excluded due to contamination and poor assembly.