Biology subjects

Mutreja, A.

Publications and source records attributed to Mutreja, A..

6 recordsLinked to original sources

bioRxiv2023

Recent emergence of cephalosporin resistant Salmonella Typhi carrying IncFIB(K) plasmid encoding blaCTX-M-15 gene in India

The emergence and spread of Salmonella Typhi (S. Typhi) resistant to third-generation cephalosporins is a serious global health concern. In this study, we genomically characterized 142 cephalosporin-resistant S. Typhi strains isolated from India. Comparative genome analysis revealed the emergence of a new clone of ceftriaxone-resistant S. Typhi harboring three plasmids of the incompatibility groups IncFIB(K), IncX1, and IncFIB(pHCM2). Among these, the IncFIB(K) plasmid confers resistance to third-generation cephalosporins through the blaCTX-M-15 gene, along with other resistance determinants such as aph(3"), aph(6), sul2, dfrA14, qnrS, and tetA. Phylogenetic analysis showed that the isolates from Gujarat (n=140/142) belong to a distinct subclade (genotype 4.3.1.2.2) within genotype 4.3.1.2 (H58 lineage II). SNP-based phylogenetic analysis of the core genes in IncFIB(K) reveals a close genetic relationship between the plasmid backbone and that of IncFIB(K) from other Enterobacterales, suggesting that the H58 lineage II possesses the capability to acquire MDR plasmids from these organisms. This could indicate the potential onset of a new wave of ceftriaxone-resistant S. Typhi in India. The implementation of control measures such as vaccination, and improved water, sanitation, and hygiene (WASH) systems, is crucial in areas where MDR or XDR S. Typhi strains are prevalent to curb the spread and impact of these resistant strains. ImportanceTyphoid fever remains a significant public health problem in many parts of the world, particularly in resource-limited settings with inadequate sanitation and limited access to clean water. The emergence of MDR S. Typhi resistant to first-line antibiotics (chloramphenicol, ampicillin, and cotrimoxazole) and fluoroquinolones marked the initial treatment challenge, leading to reliance on azithromycin and third-generation cephalosporins. Recently, researchers identified the emergence of XDR typhoid in Pakistan that is resistant to five classes of antibiotics including third-generation cephalosporins. In this study, we report a recent emergence of S. Typhi isolates resistant to third-generation cephalosporins. Genomic characterization and evolutionary analysis of the new strains revealed a recent acquisition of blaCTX-M carrying IncFIB(K) plasmid led to the emergence of ceftriaxone-resistant S. Typhi. Due to the ongoing nature of this outbreak, the data from this study deserves further consideration in order to control its spread in India.

genomics↗

bioRxiv2022

Genomic analysis unveils the role of genome degradation events and gene flux in the emergence and persistence of S. Paratyphi A lineages

Paratyphoid fever caused by S. Paratyphi A is endemic in parts of Asia and Sub-Saharan Africa. The proportion of enteric fever cases caused by S. Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory of S. Paratyphi A isolates collected as part of the Indian enteric fever surveillance study "Surveillance of Enteric Fever in India (SEFI)." In the study period (2017-2020), S. Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the global S. Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis documented that the genome degradation events and gene acquisitions or losses play a major role in the evolution of new S. Paratyphi A lineages/sub-lineages. A total of 10 pseudogene-forming mutations possibly associated with the emergence of lineages were identified. Pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3.2/2.3.3 and 1.2.2 genotypes, respectively. We also identified that the six characteristic missense mutations associated with the lipopolysaccharide (LPS) biosynthesis genes of S. Paratyphi A confer only a low structural impact and would therefore have minimal impact on vaccine effectiveness. Since S. Paratyphi A is human restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and intervention by means of genomic surveillance would be continually needed to avoid S. Paratyphi A serovar becoming a public health threat similar to the S. Typhi of today.

genomics↗

bioRxiv2020

Evolutionary tracking of SARS-CoV-2 genetic variants highlights intricate balance of stabilizing and destabilizing mutations

The currently ongoing COVID-19 pandemic caused by SARS-CoV-2 has accounted for millions of infections and deaths across the globe. Genome sequences of SARS-CoV-2 are being published daily in public databases and the availability of this genome datasets has allowed unprecedented access into the mutational patterns of SARS-CoV-2 evolution. We made use of the same genomic information for conducting phylogenetic analysis and identifying lineage-specific mutations. The catalogued lineage defining mutations were analysed for their stabilizing or destabilizing impact on viral proteins. We recorded persistence of D614G, S477N, A222V V1176F variants and a global expansion of the PANGOLIN variant B.1. In addition, a retention of Q57H (B.1.X), R203K/G204R (B.1.1.X), T85I (B.1.2-B.1.3), G15S+T428I (C.X) and I120F (D.X) variations was observed. Overall, we recorded a striking balance between stabilizing and destabilizing mutations, therefore well-maintained protein structures. With selection pressures in the form of newly developed vaccines and therapeutics to mount soon in coming months, the task of mapping of viral mutations and recording of their impact on key viral proteins would be crucial to pre-emptively catch any escape mechanism that SARS-CoV-2 may evolve for. STUDY IMPORTANCEAs large numbers of the SARS CoV-2 genome sequences are shared in publicly accessible repositories, it enables scientists a detailed evolutionary analysis since its initial isolation in Wuhan, China. We investigated the evolutionarily associated mutational diversity overlaid on the major phylogenetic lineages circulating globally, using 513 representative genomes. We detailed phylogenetic persistence of key variants facilitating global expansion of the PANGOLIN variant B.1, including the recent, fast expanding, B.1.1.7 lineage. The stabilizing or destabilizing impact of the catalogued lineage defining mutations on viral proteins indicates their possible involvement in balancing the protein function and structure. A clear understanding of this mutational profile is of high clinical significance to catch any vaccine escape mechanism, as the same proteins make crucial components of vaccines recently approved and in development. In this direction, our study provides an imperative framework and baseline data upon which further analysis could be built as newer variants of SARS-CoV-2 continue to appear.

genomics↗

bioRxiv2020

Salmonella Typhi acquires diverse plasmids from other Enterobacteriaceae to develop cephalosporin resistance

BackgroundRecent reports have established the emergence and dissemination of extensively drug resistant (XDR) H58 Salmonella Typhi clone in Pakistan. In India where typhoid fever is endemic, only sporadic cases of ceftriaxone resistant S. Typhi are reported. This study aimed at elucidating the phylogenetic evolutionary framework of ceftriaxone resistant S. Typhi isolates from India to predict their potential dissemination in endemic regions. MethodsFive ceftriaxone resistant S. Typhi isolates from three tertiary care hospitals in India were sequenced on an Ion Torrent Personal Genome Machine (PGM). A core genome single-nucleotide-polymorphism (SNP) based phylogeny of the isolates in comparison to the global collection of MDR and XDR S. Typhi isolates was built. Two of five isolates were additionally sequenced using Oxford Nanopore MinION to completely characterize the plasmid and understand its transmission dynamics within Enterobacteriaceae. ResultsComparative genomic analysis and detailed plasmid characterization indicate that while in Pakistan (4.3.1 lineage I) the XDR trait is associated with blaCTX-M-15 gene on IncY plasmid, in India (4.3.1 lineage II), the ceftriaxone resistance is due to short term adaptation of resistance plasmids such as IncX3 or IncN. ConclusionSince the bacterial acquisition of smaller resistance plasmids such as IncX3 or IncN from other Enterobacteriaceae can be much faster than the larger IncY plasmids, the rapid expansion of these genotypically novel XDR S. Typhi could potentially cause large outbreaks. Therefore, continuous monitoring of S. Typhi lineages carrying cephalosporin resistance on IncX3 or IncN plasmids is vital not just for India but globally. ImportanceGenomic analysis of cephalosporin resistant S. Typhi isolated from India indicates the potential of S. Typhi to develop cephalosporin resistance by acquiring diverse plasmids from other Enterobacteriaceae. We identified the occurrence of independent acquisition of drug-resistant plasmids such as IncX3 and IncN with genes encoding beta-lactamases in H58/4.3.1.2 lineage. A short term adaptation of drug-resistant plasmids in H58/4.3.1.2 lineage can be the reason for the sporadic cases cephalosporin resistant S. Typhi in India. However, the IncY plasmid acquired by isolates that belong to H58/4.3.1.1 lineage appeared to be well adapted as observed in XDR S. Typhi outbreak in Pakistan. Plasmid acquisition and maintenance of cephalosporin resistant S. Typhi appears to be specific to the phylogenetic lineage as lineages differ in compensating the initial cost imposed by the plasmid. The stable maintenance of these resistance plasmids without a fitness cost, are determinant in understanding the future spread of cephalosporin resistance in S. Typhi. Therefore, critical strategies in monitoring and control of cephalosporin resistant S. Typhi is needed to tackle further public health crisis.

genomics↗

bioRxiv2020

Phylogenetic and evolutionary analysis reveals the recent dominance of ciprofloxacin resistant S. sonnei and local persistence of S. flexneri clones in India

Shigella is the second leading cause of bacterial diarrhea worldwide. Recently S. sonnei seems to be replacing S. flexneri in low and middle-income countries undergoing economic development. Despite this, studies focusing on these species at genomic level remain largely unexplored. Here we compared the genome sequences of S. flexneri and S. sonnei isolated from India with the publically available genomes of global strains. Our analysis provide evidence for the long term persistence of all PGs of S. flexneri and the recent dominance of ciprofloxacin-resistant S. sonnei lineage in India. Within S. flexneri PGs, majority of the study isolates belonged to PG3 within the predominance of serotype 2. For S. sonnei, the current pandemic involves globally distributed MDR clones that belong to Central Asia lineage III. The presence of such epidemiologically-dominant lineages in association with stable AMR determinants results in the successful survival in the community.

genomics↗

bioRxiv2019

First Indian report on Genome-wide Comparison of Multidrug-Resistant Escherichia coli from Blood Stream Infections

BackgroundMultidrug-resistant (MDR) E. coli with extended-spectrum {beta}-lactamases (ESBLs) is becoming endemic in health care settings around the world. Baseline data on virulence and AMR of specific lineages of E. coli circulating in developing countries like India is currently lacking.\n\nMethodsWhole-genome sequencing was performed for 60 MDR E. coli isolates. Genome-wide analysis was performed at single nucleotide polymorphism (SNP) level resolution to identify the relation between the isolates in context of time, virulence and AMR determinants possessed.\n\nResultsGenome comparison revealed the presence of ST-131 global MDR and ST410 as emerging-MDR clades of E. coli. AMR gene profile for cephalosporin and carbapenem resistance differed between the clades. Genotypes blaCTX-M-15 and blaNDM-5 were common among cephalosporinases and carbapenemases, respectively. For aminoglycoside resistance, rmtB was positive for 31.7% of the isolates, of which 30% were co-harboring carbapenemases. Further, the FimH types and virulence gene profile positively correlated with the SNP based phylogeny, which also revealed the evolution of MDR clones among the study population with temporal accumulation of SNPs. The predominant clone was ST167 (blaNDM lineage) followed by ST405 (global clone ST131 equivalent) and ST410 (fast spreading high risk clone).\n\nConclusionsThis is the first report on the whole genome analysis of MDR E. coli lineages circulating in India. Data from this study will provide public health agencies a baseline portfolio of AMR and virulence in pathogenic E. coli in the region.

genomics↗