The discovery of antibiotics in the last century is considered one of the most important achievements in the history of medicine. Antibiotic usage has significantly reduced morbidity and mortality associated with bacterial infections. However, inappropriate use of antibiotics has led to emergence of antibiotic resistance at an alarming rate. Antibiotic resistance is regarded as a major health care challenge of this century. Despite extensive research, well-documented biochemical mechanisms and genetic changes fail to fully explain mechanisms underlying antibiotic resistance. Several recent reports suggest a key role for epigenetics in the development of antibiotic resistance in bacteria. The intrinsic heterogeneity as well as transient nature of epigenetic inheritance provides a plausible backdrop for high-paced emergence of drug resistance in bacteria. The methylation of adenines and cytosines can influence mutation rates in bacterial genomes, thus modulating antibiotic susceptibility. In this review, we discuss a plethora of recently discovered epigenetic mechanisms and their emerging roles in antibiotic resistance. We also highlight specific epigenetic mechanisms that merit further investigation for their role in antibiotic resistance.

Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Numerous reports indicate an oncogenic role for HBV-encoded HBsAg; however, the underlying mechanisms are not well understood.

Background Urinary tract infection (UTI) in children is a common bacterial infection. The emergence of extended-spectrum beta-lactamases (ESBLs) poses a major challenge against the treatment of uropathogens. We aimed to characterize the E. coli isolates recovered from children with UTI for their resistance profile and circulating sequence types (ST). Methods Children (> 1.5–18 years of age) from different community health centres of India with symptoms of UTI were enrolled. Isolates causing significant bacteriuria were identified by Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) and tested for antimicrobial susceptibility by the automated system, VITEK-2 (Biomeriux, Durhum, US). Nineteen E. coli isolates (15 ESBL positive and 4 ESBL negative) were sequenced in Oxford Nanopore platform followed by core-genome phylogeny, accessory genome cluster analysis, identification of sequence types, mobile genetic elements, genetic antimicrobial resistance markers. The correlation between detection of antimicrobial resistance genes with phenotypic resistance profiles was also investigated. Results Eleven percent of children had significant bacteriuria [male:female—1:1, > 50% were 11–18 years of age group]. E. coli was predominant (86%) followed by K. pneumoniae (11%). Susceptibility of E. coli was highest against fosfomycin (100%) followed by carbapenems (90.7%) and nitrofurantoin (88.8%). ST131 (15.8%) and ST167 (10.5%) found as high-risk clones with the presence of plasmid [IncFIB (63.1%), IncFIA (52.6%)], and composite transposon [Tn2680 (46.6%)] in many isolates. Few isolates coharboured multiple beta-lactamases including blaNDM-5 (33.3%), blaOXA-1 (53.3%), blaCTX-M-15 (60%) and blaTEM-4 (60%). Conclusions This study highlights horizontal transmission of resistance genes and plasmids in paediatric patients at community centers across the nation harbouring multidrug-resistant genes such as blaNDM-5 and blaCTX-M-15 associated with high-risk clones ST131 and ST167. The data is alarming and emphasizes the need for rapid identification of resistance markers to reduce the spread in community. To our knowledge, this is the first multicentric study targeting paediatric UTI patients from the community setting of India.

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Changes in the spatial organization of bacterial chromosomes under stress conditions and its biological implications remain poorly understood. We mapped the structural landscape of wild-type and Δdcm E. colichromosomes under triclosan stress using Hi-C to identify triclosan-induced chromosomal interaction domains (CIDs). Two CIDs were common to the wild-type and Δdcm E. coli, including a CID with a common boundary atfabIgene, which encodes the triclosan target. All mutations and structural variants under triclosan stress were observed within or in close proximity to triclosan-induced CIDs. Absence of Dcm methylation impacts both short- and long-range interactions in triclosan stress. Single-base resolution methylome maps reveal hypermethylation of adenines (in wild-type and Δdcm) and cytosines (in wild-type) in the two common triclosan-induced CIDs. Furthermore, global gene expression profiling identified enrichment of highly expressed genes within the two common CIDs. Our findings suggest that stress-induced CIDs inE. coliare hotspots for genetic variations and are associated with enhanced transcriptional activity and hypermethylation of Dam/Dcm motifs.