Work

Investigating the molecular transmission dynamics of bla NDM in antibiotic-selective environments

Year: 2025

Type: article

Abstract: ABSTRACT Carbapenem resistance mediated by bla NDM -encoded metallo-beta-lactamases is often linked to IS Aba125 , an insertion sequence from the IS 30 family, which is widely distributed among critical and high-priority bacterial pathogens. The rapid dissemination of IS Aba125 -linked bla NDM in both nosocomial and community-acquired infections presents a serious challenge to healthcare systems and pharmaceutical industries. Despite the urgency of this issue, the factors driving bla NDM spread and the molecular mechanisms governing IS Aba125 mobility remain poorly understood. In this study, we engineered the genomes of Vibrio cholerae and Escherichia coli to investigate the mobility of bla NDM under controlled conditions both with and without the genetically linked IS Aba125 . We also examined the transmission efficiency and the stability of bla NDM in environments with and without sublethal antibiotic concentrations. Our in vitro findings were validated in a rabbit ileal loop model. The results revealed that antibiotic pressure significantly influences the mobility of bla NDM , shedding light on the molecular dynamics of its transmission. These insights are crucial for developing strategies to curb the spread of bla NDM and mitigate the growing threat of carbapenem resistance in bacterial pathogens. IMPORTANCE Insertion sequences are the simplest form of mobile genetic elements that play a critical role in the adaptation of bacteria, allowing them to rapidly acquire new traits like resistance genes that enhance their survival. IS Aba125 is one such insertion sequence that facilitates the spread of bla NDM , contributing to the global challenge of carbapenem resistance. In this study, we developed reporter strains that could be used as a valuable tool for investigating the dynamics of IS Aba125- linked bla NDM sh-ble and evaluated the transposition frequency of IS Aba125- linked bla NDM sh-ble in the presence and absence of sublethal concentration of antibiotics. Our results demonstrated that IS Aba125 enhances the spread of bla NDM sh-ble under sublethal concentration of antibiotics that induces SOS response.

Source: Journal of Bacteriology

DOI: 10.1128/jb.00133-25

Authors: Shashi Kumari, Lekshmi Narendrakumar, Meenal Chawla, Sanjib Das, Hemanta Koley, Bhabatosh Das

Institutions: Translational Health Science and Technology Institute, Indian Council of Medical Research

Language: English

Topic: Antibiotic Resistance in Bacteria

Subfield: Molecular Medicine

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: Department of Biotechnology, Ministry of Science and Technology, India