blaCTX-M-152, a Novel Variant of CTX-M-group-25, Identified in a Study Performed on the Prevalence of Multidrug Resistance among Natural Inhabitants of River Yamuna, India

Abstract

Natural environment influenced by anthropogenic activities creates selective pressure for acquisition and spread of resistance genes. In this study, we determined the prevalence of Extended Spectrum β-Lactamases producing gram negative bacteria from the River Yamuna, India, and report the identification and characterization of a novel CTX-M gene variant blaCTX-M-152. Of the total 230 non-duplicate isolates obtained from collected water samples, 40 isolates were found positive for ESBL production through Inhibitor-Potentiation Disc Diffusion test. Based on their resistance profile, 3% were found exhibiting pandrug resistance (PDR), 47% extensively drug resistance (XDR), and remaining 50% showing multidrug resistant (MDR). Following screening and antimicrobial profiling, characterization of ESBLs (blaTEM and blaCTX-M), and mercury tolerance determinants (merP, merT, and merB) were performed. In addition to abundance of blaTEM-116 (57.5%) and blaCTX-M-15 (37.5%), bacteria were also found to harbor other variants of ESBLs like blaCTX-M-71 (5%), blaCTX-M-3 (7.5%), blaCTX-M-32 (2.5%), blaCTX-M-152 (7.5%), blaCTX-M-55 (2.5%), along with some non-ESBLs; blaTEM-1 (25%) and blaOXY (5%). Additionally, co-occurrence of mercury tolerance genes were observed among 40% of isolates. In silico studies of the new variant, blaCTX-M-152were conducted through modeling for the generation of structure followed by docking to determine its catalytic profile. CTX-M-152 was found to be an out-member of CTX-M-group-25 due to Q26H, T154A, G89D, P99S, and D146G substitutions. Five residues Ser70, Asn132, Ser237, Gly238, and Arg273 were found responsible for positioning of cefotaxime into the active site through seven H-bonds with binding energy of -7.6 Kcal/mol. Despite small active site, co-operative interactions of Ser237 and Arg276 were found actively contributing to its high catalytic efficiency. To the best of our knowledge, this is the first report of blaCTX-M-152 of CTX-M-group-25 from Indian subcontinent. Taking a note of bacteria harboring such high proportion of multidrug and mercury resistance determinants, their presence in natural water resources employed for human consumption increases the chances of potential risk to human health. Hence, deeper insights into mechanisms pertaining to resistance development are required to frame out strategies to tackle the situation and prevent acquisition and dissemination of resistance determinants so as to combat the escalating burden of infectious diseases.

Prevalence and Molecular Characterization of ESBL Producing Enterobacteriaceae from Highly Polluted Stretch of River Yamuna, India

“…The co-existence of more than one β-lactamase gene within the same isolate is well documented in several studies [42,43]. The combination of bla CTX-M-15 + bla TEM-116 found in 12 isolates and bla CTX-M-15 + bla TEM-1 in 11 isolates had also been previously reported in E. coli by Azam et al and Al-Agamy et al, respectively [14,44].…”

“…In the present study, 34.58% of bacterial isolates from heavily polluted Delhi stretch of river Yamuna, India were found to be ESBL producers conferring resistance to cephalosporins. This high prevalence of ESBL positive Enterobacteria-ceae was more than previous reports on E. coli and other gram negative bacteria from river Yamuna [14,15]. Moreover, studies from rivers (n = 40) and lakes (n = 18) of Switzerland and rivers (n = 15) of Taiwan reported more or less similar prevalence (36.2% Enterobacteriaceae and 30% E. coli, respectively) of ESBL producing isolates [18,19].…”

“…CTX-M-152, a variant of CTX-M-group-25, first identified in India in Kluvyera georgiana was detected in bacterial isolates of A. baumannii, A. variabilis, A. junii and Shigella sp. [14].…”

Antimicrobial resistance: Call for rational antibiotics practice in India

“…[ 61 ] The ESBL producers were 17.4% among bacteria (Gram-negative) isolated from Yamuna and Ganga. [ 62 ]…”

Mass bathing events in River Kshipra, Central India- influence on the water quality and the antibiotic susceptibility pattern of commensal E.coli

“…Occurrence of antibiotic resistant bacteria has been reported from different rivers of India [12][13][14]. It is important to develop knowledge about the role and dynamicity of presence of antibiotic resistance in river-water during mass gatherings to design approaches to contain antibiotic resistance in rivers.…”