Biology subjects

Jabeen, K.

Publications and source records attributed to Jabeen, K..

3 recordsLinked to original sources

bioRxiv2024

Genomic characterization of plasmids harboring blaNDM-1,-5,-7 carbapenemase alleles in clinical Klebsiella pneumoniae in Pakistan

Klebsiella pneumoniae is notorious for causing healthcare-associated infections, which become more complicated by the acquisition of blaNDM genes via mobile genetic elements. Although Pakistan is a well-established hot spot of blaNDM-positive K. pneumoniae, detailed molecular descriptions of blaNDM-carrying plasmids are scarce. Seven K. pneumoniae isolates harboring blaNDM were recovered from clinical sample sources during a six-month period and tested for antimicrobial susceptibility. A long-read approach was used for whole genome sequencing to obtain circularized plasmids and chromosomes for typing, annotation, and comparative analysis. The isolates were susceptible to colistin and tigecycline only among the tested antibiotics. We identified five STs: ST11, ST16, ST716, ST464, and ST2856. Notably, three strains possessed the hypervirulent capsule KL2, while five were classified as O locus type O2a. Evidence of genetic diversity was further highlighted by the presence of four IncC plasmids harboring blaNDM-1, two IncX3 plasmids harboring blaNDM-5, and a single hybrid IncFIB/IncHI1B plasmid harboring blaNDM-7. These plasmids also carried additional ARGs conferring resistance to aminoglycosides, cephalosporins, and fluoroquinolones. We identified the plasmidome of the K. pneumoniae isolates and characterized the NDM-carrying plasmids. Genetic analysis confirmed the presence of blaNDM-1 and blaNDM-5 on broad host range plasmids and blaNDM-7 in a previously unreported hybrid plasmid backbone. We emphasized the critical role of plasmids in spreading blaNDM in the clinical setting in Pakistan. Hence, we stressed the urgent need for enhanced surveillance, not least in LMICs, infection control measures, and adherence to the AWaRe guidelines in antibiotics use.

microbiology↗

bioRxiv2023

Overlooked Candida glabrata petites are echinocandin tolerant, induce host inflammatory responses, and display poor in vivo fitness

Small colony variants (SCVs) are relatively common among some bacterial species and are associated with poor prognosis and recalcitrant infections. Similarly, Candida glabrata - a major intracellular fungal pathogen - produces small and slow-growing respiratory-deficient colonies, termed "petite." Despite reports of clinical petite C. glabrata strains, our understanding of petite behavior in the host remains obscure. Moreover, controversies exist regarding in-host petite fitness and its clinical relevance. Herein, we employed whole-genome sequencing (WGS), dual-RNAseq, and extensive ex vivo and in vivo studies to fill this knowledge gap. WGS identified multiple petite-specific mutations in nuclear and mitochondrially-encoded genes. Consistent with dual-RNAseq data, petite C. glabrata cells did not replicate inside host macrophages and were outcompeted by their non-petite parents in macrophages and in gut colonization and systemic infection mouse models. The intracellular petites showed hallmarks of drug tolerance and were relatively insensitive to the fungicidal activity of echinocandin drugs. Petite-infected macrophages exhibited a pro-inflammatory and type I IFN-skewed transcriptional program. Interrogation of international C. glabrata blood isolates (n=1000) showed that petite prevalence varies by country, albeit at an overall low prevalence (0-3.5%). Collectively, our study sheds new light on the genetic basis, drug susceptibility, clinical prevalence, and host-pathogen responses of a clinically overlooked phenotype in a major fungal pathogen. ImportanceCandida glabrata is a major fungal pathogen, which is able to lose mitochondria and form small and slow-growing colonies, called "petite". This attenuated growth rate has created controversies and questioned the clinical importance of petiteness. Herein, we have employed multiple omicstechnologies and in vivo mouse models to critically assess the clinical importance of petite phenotype. Our WGS identifies multiple genes potentially underpinning petite phenotype. Interestingly, petite C. glabrata cells engulfed by macrophages are dormant and therefore are not killed by the frontline antifungal drugs. Interestingly, macrophages infected with petite cells mount distinct transcriptomic responses. Consistent with our ex-vivo observations, mitochondrial-proficient parental strains outcompete petites during systemic and gut colonization. Retrospective examination of C. glabrata isolates identified petite prevalence a rare entity, can significantly vary from country to country. Collectively, our study overcomes the existing controversies and provides novel insights regarding the clinical relevance of petite C. glabrata isolates.

microbiology↗

bioRxiv2020

Naringenin downregulates inflammation-mediated nitric oxide overproduction and potentiates endogenous antioxidant status during hyperglycemia

Nitric oxide (NO) is a key regulating factor for physiological functions, when elevated during inflammatory conditions can lower endogenous antioxidant levels. Increased NO interacts with oxygen or other ROS to generate peroxynitrite, a potent oxidant which induces oxidative stress. Analgesic effects of naringenin (NRN), a flavanone has been demonstrated by inducing anti-inflammatory effects in O2-*-mediated inflammation. NRN stimulates antioxidant enzymes and also improves glucose uptake. Hence this study was designed to look for therapeutic effects of NRN and in comparison, to metformin (MET) on inflammation-mediated increased NO and decreased antioxidant superoxide dismutase (SOD) in diabetic rat model with compromised glycemic and lipid profile. After single intraperitoneal injection of alloxan (120 mg/kg), the rats were equally divided as Group 1 and 2 which received normal saline and no-treatment respectively while group 3 and 4 received MET 50 mg/kg/day and NRN 50 mg/kg/day respectively. Blood samples were collected at 0, 15th and 30th day of treatment period. Results showed that alloxan significantly increased serum level of glucose (P<0.001), NO (P<0.001) and inflammatory biomarkers (TNF-, IL-6), however, it expressively decreased serum SOD and insulin level. While, NRN significantly downregulated glucose (P<0.05), lipid profile, TNF-, IL-6 and normalized level of NO (P<0.01). It also improved SOD level as compared to that of MET-treatment. Histopathology of pancreas also showed significant improvement in morphology after NRN treatment. This work delivers that NRN exerts anti-oxidant effect in part by downregulating the inflammation-mediated NO overproduction and improving level of SOD resulting in potentiation of endogenous antioxidant defense.

biochemistry↗