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1.
Bioinformatics ; 39(11)2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37947313

RESUMEN

MOTIVATION: Fungal pathogens are known to cause life threatening invasive infections with rising global mortality rates. Besides, the indiscriminate use of antifungals in both clinics and agriculture has promoted antifungal drug resistance in the last decade. Fungi can show drug resistance by a variety of mechanisms. But primary driver in all these hitherto documented mechanisms is stable and heritable point mutations in the key proteins. Therefore, cataloguing mutations that can confer resistance is the first step toward understanding the mechanisms leading to the emergence of antifungal resistance. RESULTS: In the present, work we have described a database of all the mutations responsible for antifungal resistance. Named as antifungal resistance database (AFRbase), it is better than the existing databases of antifungal resistance namely, FunResDB and MARDy which have a limited scope and inadequate information. Data of AFRbase was collected using both text mining and manual curation. AFRbase provides a separate window for visualization of mutations in the 2D and 3D formats making it easy for researchers to analyze the mutation data and ensures interoperability with other standard molecular biology databases like NCBI and UniProtKB. We hope AFRbase can be useful to both clinicians and basic biomedical scientists as we envision it as an important resource for genotypic susceptibility testing of fungi and to study/predict the course of evolution of antifungal resistance. The current version of AFRbase contains manually curated 3691 unique mutations present in 29 proteins of 32 fungal species along with the information of drugs against which resistance is caused. AVAILABILITY AND IMPLEMENTATION: AFRbase is an open access database available at http://proteininformatics.org/mkumar/afrbase/.


Asunto(s)
Antifúngicos , Farmacorresistencia Fúngica , Antifúngicos/farmacología , Bases de Datos Factuales , Mutación , Farmacorresistencia Fúngica/genética
2.
Brief Bioinform ; 22(3)2021 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-32895696

RESUMEN

Mycobacterium avium subspecies paratuberculosis (MAP) exhibits 'molecular mimicry' with the human host resulting in several autoimmune diseases such as multiple sclerosis, type 1 diabetes mellitus (T1DM), Hashimoto's thyroiditis, Crohn's disease (CD), etc. The conventional therapy for autoimmune diseases includes immunosuppressants or immunomodulators that treat the symptoms rather than the etiology and/or causative mechanism(s). Eliminating MAP-the etiopathological agent might be a better strategy to treat MAP-associated autoimmune diseases. In this case study, we conducted a systematic in silico analysis to identify the metabolic chokepoints of MAP's mimicry proteins and their interacting partners. The probable inhibitors of chokepoint proteins were identified using DrugBank. DrugBank molecules were stringently screened and molecular interactions were analyzed by molecular docking and 'off-target' binding. Thus, we identified 18 metabolic chokepoints of MAP mimicry proteins and 13 DrugBank molecules that could inhibit three chokepoint proteins viz. katG, rpoB and narH. On the basis of molecular interaction between drug and target proteins finally eight DrugBank molecules, viz. DB00609, DB00951, DB00615, DB01220, DB08638, DB08226, DB08266 and DB07349 were selected and are proposed for treatment of three MAP-associated autoimmune diseases namely, T1DM, CD and multiple sclerosis. Because these molecules are either approved by the Food and Drug Administration or these are experimental drugs that can be easily incorporated in clinical studies or tested in vitro. The proposed strategy may be used to repurpose drugs to treat autoimmune diseases induced by other pathogens.


Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Simulación por Computador , Mycobacterium avium subsp. paratuberculosis/efectos de los fármacos , Paratuberculosis/tratamiento farmacológico , Preparaciones Farmacéuticas/administración & dosificación , Animales , Enfermedades Autoinmunes/metabolismo , Enfermedades Autoinmunes/microbiología , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/microbiología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/microbiología , Interacciones Huésped-Patógeno , Humanos , Simulación del Acoplamiento Molecular , Terapia Molecular Dirigida/métodos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/microbiología , Mycobacterium avium subsp. paratuberculosis/metabolismo , Mycobacterium avium subsp. paratuberculosis/fisiología , Paratuberculosis/metabolismo , Paratuberculosis/microbiología , Unión Proteica , Mapas de Interacción de Proteínas/efectos de los fármacos
3.
Nucleic Acids Res ; 48(W1): W239-W243, 2020 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-32421834

RESUMEN

Recent evidences suggest that the localization of mRNAs near the subcellular compartment of the translated proteins is a more robust cellular tool, which optimizes protein expression, post-transcriptionally. Retention of mRNA in the nucleus can regulate the amount of protein translated from each mRNA, thus allowing a tight temporal regulation of translation or buffering of protein levels from bursty transcription. Besides, mRNA localization performs a variety of additional roles like long-distance signaling, facilitating assembly of protein complexes and coordination of developmental processes. Here, we describe a novel machine-learning based tool, mRNALoc, to predict five sub-cellular locations of eukaryotic mRNAs using cDNA/mRNA sequences. During five fold cross-validations, the maximum overall accuracy was 65.19, 75.36, 67.10, 99.70 and 73.59% for the extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. Assessment on independent datasets revealed the prediction accuracies of 58.10, 69.23, 64.55, 96.88 and 69.35% for extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. The corresponding values of AUC were 0.76, 0.75, 0.70, 0.98 and 0.74 for the extracellular region, endoplasmic reticulum, cytoplasm, mitochondria, and nucleus, respectively. The mRNALoc standalone software and web-server are freely available for academic use under GNU GPL at http://proteininformatics.org/mkumar/mrnaloc.


Asunto(s)
ARN Mensajero/análisis , Programas Informáticos , Máquina de Vectores de Soporte , Núcleo Celular/química , Simulación por Computador , Citoplasma/química , Retículo Endoplásmico/química , Mitocondrias/química , ARN Mensajero/química , Análisis de Secuencia de ARN
4.
Indian J Microbiol ; 59(1): 112-115, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30728640

RESUMEN

The enormous health benefits associated with probiotics has resulted in an increased consumption of probiotic supplements. Several factors like regular sub-culturing, storage, unfavourable conditions etc. might compromise the efficacy and/or safety of lactic acid bacteria which are the major components of many probiotic preparations available in the market. The present study evaluated the probiotic characteristics and safety of probiotic bacteria isolated from two preparations available commercially in India. The products did not specify the genera, species or strains of the bacteria used. These were cultured using standard microbiological methods for cultivation of lactic acid bacteria. Bacteria were identified by PCR amplification and sequence analysis of 16S rRNA gene. Microbiological and molecular analyses revealed that both preparations contained homogenous population of Enterococcus faecium and Pediococcus acidilactici respectively. Assessment for several essential and desirable probiotic properties revealed that both the probiotic strains were safe and resistant to salt, lysozyme, bile salt and common antibiotics. The probiotic preparation containing P. acidilactici was better than that containing E. faecium as it survived in low pH and showed bile salt hydrolase activity. The probiotic preparation containing P. acidilactici also exhibited cholesterol-lowering activity.

6.
Parasitology ; 143(12): 1491-500, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27387025

RESUMEN

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is currently being used for rapid and reproducible identification of bacteria, viruses and fungi in clinical microbiological laboratories. However, some studies have also reported the use of MALDI-TOF MS for identification of parasites, like Leishmania, Giardia, Cryptosporidium, Entamoeba, ticks and fleas. The present review collates all the information available on the use of this technique for parasites, in an effort to assess its applicability and the constraints for identification/diagnosis of parasites and diseases caused by them. Though MALDI-TOF MS-based identification of parasites is currently done by reference laboratories only, in future, this promising technology might surely replace/augment molecular methods in clinical parasitology laboratories.


Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Pruebas Diagnósticas de Rutina/métodos , Parasitología/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Humanos , Enfermedades Parasitarias/diagnóstico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/estadística & datos numéricos
7.
ScientificWorldJournal ; 2014: 980572, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24678282

RESUMEN

Beta-lactamases are a superfamily of enzymes which degrade the ß-lactam class of antibiotics. They are produced endogenously by the bacterial cells, which when exposed to the ß-lactam class of antibiotics inactivate them by cleaving the ß-lactam ring. Based on the presence or absence of metallic ligand, ß-lactamases have been divided into two broad functional classes. ß-Lactamases are a constitutively evolving and expanding superfamily of enzymes, which could be further subdivided on the basis of presence/absence of conserved motifs. In the present study we have used the MEME/MAST suit to identify the patterns/motifs which are specific to a particular family or subfamily of ß-lactamases. The family specific patterns/motifs can be also useful in recognizing and assigning newly discovered ß-lactamases to one or the other family or subfamily. Cross-validation showed that the proposed method is highly sensitive and specific. We have also designed a webserver, LactFP, for this purpose.


Asunto(s)
Bacterias/clasificación , Bacterias/genética , Huella de ADN , beta-Lactamasas/genética , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Biología Computacional , Bases de Datos Genéticas , Farmacorresistencia Bacteriana/genética , Posición Específica de Matrices de Puntuación , Reproducibilidad de los Resultados , Navegador Web , beta-Lactamasas/química
8.
Sci Data ; 10(1): 573, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37658065

RESUMEN

Escherichia coli are highly diverse bacteria with different pathogenic types, serotypes and phylogenetic types/phylotypes. In recent years, infections with E. coli have increased worldwide and so has the emergence of antibiotic resistant strains. In the present study we have assembled, annotated and analysed genome sequences of three strains of the phylogroup D of E. coli. These strains were isolated from the river Yamuna, a prominent anthropogenic urban river of northern India. These strains showed varied antibiotic susceptibilities, one was susceptible to all the antibiotics tested except ampicillin while of the other two, one was multi-ß-lactam resistant and the other was multi-drug resistant (resistant to multiple ß-lactams, fluoroquinolones and kanamycin). The short-sequence reads were assembled into contigs using the de-novo approach and further, scaffolding of contigs was performed by using the best reference genome for a particular isolate which resulted in a significant increase in the N50 value of each assembly. The bioinformatics assembly approach used in this study could be easily applied to study other bacterial genomes.


Asunto(s)
Escherichia coli , Genómica , Antibacterianos , Biología Computacional , Filogenia
9.
Front Nutr ; 10: 1082566, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37081914

RESUMEN

Hypercholesterolemia is a major risk factor for cardiovascular diseases (CVDs). Chemotherapeutic agents for CVDs exhibit several side effects. Specific probiotics with hypocholesterolemic effects can be safe and effective alternatives to chemotherapeutics. Here, we have analyzed and compared the genome of a novel rhizospheric Enterococcus faecium LR13 cholesterol-assimilating probiotic with other probiotic/pathogenic E. faecium strains to discern genetic factors underlying probiotic efficacy and cholesterol-assimilation. Genomic analyses of E. faecium probiotic strains revealed that LR13 and WEFA23 (cholesterol-assimilating probiotics) harbored 21 unique proteins absent in non-cholesterol-assimilating probiotics. Of these, 14 proteins could directly help in cholesterol-assimilation by producing short chain fatty acids, lipid (sterol) transport and membrane stabilization, and bile salt hydrolase activity. This suggests that cholesterol-assimilation is an intrinsic, strain-specific trait exhibited by probiotics with a specific genetic constitution. Moreover, the unique proteins identified in this study can serve as biomarkers for discerning/characterizing cholesterol-assimilating probiotics as novel biotherapeutics against CVDs.

10.
Proteome Sci ; 10(1): 14, 2012 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-22375954

RESUMEN

BACKGROUND: Tuberculosis (TB) is the most threatening infectious disease globally. Although progress has been made to reduce global incidence of TB, emergence of multidrug resistant (MDR) TB threatens to undermine these advances. To combat the disease, novel intervention strategies effective against drug resistant and sensitive subpopulations of M. tuberculosis are urgently required as adducts in the present treatment regimen. Using THP-1 cells we have analyzed and compared the global protein expression profile of broth-cultured and intraphagosomally grown drug resistant and sensitive M.tuberculosis clinical isolates. RESULTS: On comparing the two dimensional (2-DE) gels, many proteins were found to be upregulated/expressed during intracellular state which were identified by matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). Four proteins (adenosylhomocysteinase, aspartate carbomyltransferase, putatitive thiosulfate sulfurtransferase and universal stress protein) were present in both intracellular MDR and sensitive isolates and three of these belonged to intermediary metabolism and respiration category. Two proteins (alanine dehydrogenase and adenosine kinase) of intracellular MDR isolate and two (glucose-6-phosphate isomerase and ATP synthase epsilon chain) of intracellular sensitive isolate belonged to intermediary metabolism and respiration category. One protein (Peroxidase/Catalase) of intracellular MDR and three (HSPX, 14 kDa antigen and 10 kDa chaperonin) of sensitive isolate belonged to virulence, detoxification and adaptation category. ESAT-6 of intracellular MDR belonged to cell wall and cell processes category. Two proteins (Antigen 85-C and Antigen 85-A) of intracellular sensitive isolate were involved in lipid metabolism while probable peptidyl-prolyl cis-trans isomerase A was involved in information pathways. Four (Rv0635, Rv1827, Rv0036c and Rv2032) of intracellular MDR and two proteins (Rv2896c and Rv2558c) of sensitive isolate were hypothetical proteins which were functionally characterized using bioinformatic tools. Bioinformatic findings revealed that the proteins encoded by Rv0036, Rv2032c, Rv0635, Rv1827 and Rv2896c genes are involved in cellular metabolism and help in intracellular survival. CONCLUSIONS: Mass spectrometry and bioinformatic analysis of both MDR and sensitive isolates of M. tuberculosis during intraphagosomal growth showed that majority of commonly upregulated/expressed proteins belonged to the cellular metabolism and respiration category. Inhibitors of the metabolic enzymes/intermediate can therefore serve as suitable drug targets against drug-resistant and sensitive subpopulations of M. tuberculosis.

11.
Front Microbiol ; 13: 1039687, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36713195

RESUMEN

ß-Lactams are a broad class of antimicrobial agents with a high safety profile, making them the most widely used class in clinical, agricultural, and veterinary setups. The widespread use of ß-lactams has induced the extensive spread of ß-lactamase hydrolyzing enzymes known as ß-lactamases (BLs). To neutralize the effect of ß-lactamases, newer generations of ß-lactams have been developed, which ultimately led to the evolution of a highly diverse family of BLs. Based on sequence homology, BLs are categorized into four classes: A-D in Ambler's classification system. Further, each class is subdivided into families. Class B is first divided into subclasses B1-B3, and then each subclass is divided into families. The class to which a BL belongs gives a lot of insight into its hydrolytic profile. Traditional methods of determining the hydrolytic profile of BLs and their classification are time-consuming and require resources. Hence we developed a machine-learning-based in silico method, named as ß-LacFamPred, for the prediction and annotation of Ambler's class, subclass, and 96 families of BLs. During leave-one-out cross-validation, except one all ß-LacFamPred model HMMs showed 100% accuracy. Benchmarking with other BL family prediction methods showed ß-LacFamPred to be the most accurate. Out of 60 penicillin-binding proteins (PBPs) and 57 glyoxalase II proteins, ß-LacFamPred correctly predicted 56 PBPs and none of the glyoxalase II sequences as non-BLs. Proteome-wide annotation of BLs by ß-LacFamPred showed a very less number of false-positive predictions in comparison to the recently developed BL class prediction tool DeepBL. ß-LacFamPred is available both as a web-server and standalone tool at http://proteininformatics.org/mkumar/blacfampred and GitHub repository https://github.com/mkubiophysics/B-LacFamPred respectively.

12.
PLoS One ; 17(4): e0265657, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35421114

RESUMEN

Microbial mimicry of the host proteins/peptides can elicit host auto-reactive T- or B-cells resulting in autoimmune disease(s). Since intrinsically disordered protein regions (IDPRs) are involved in several host cell signaling and PPI networks, molecular mimicry of the IDPRs can help the pathogens in substituting their own proteins in the host cell-signaling and PPI networks and, ultimately hijacking the host cellular machinery. Thus, the present study was conducted to discern the structural disorder and intrinsically disordered protein regions (IDPRs) like, molecular recognition features (MoRFs), short linear motifs (SLiMs), and low complexity regions (LCRs) in the experimentally verified mimicry proteins and peptides (mimitopes) of bacteria, viruses and host. Also, functional characteristics of the mimicry proteins were studied in silico. Our results indicated that 78% of the bacterial host mimicry proteins and 45% of the bacterial host mimitopes were moderately/highly disordered while, 73% of the viral host mimicry proteins and 31% of the viral host mimitopes were moderately/highly disordered. Among the pathogens, 27% of the bacterial mimicry proteins and 13% of the bacterial mimitopes were moderately/highly disordered while, 53% of the viral mimicry proteins and 21% of the viral mimitopes were moderately/highly disordered. Though IDPR were frequent in host, bacterial and viral mimicry proteins, only a few mimitopes overlapped with the IDPRs like, MoRFs, SLiMs and LCRs. This suggests that most of the microbes cannot use molecular mimicry to modulate the host PPIs and hijack the host cell machinery. Functional analyses indicated that most of the pathogens exhibited mimicry with the host proteins involved in ion binding and signaling pathways. This is the first report on the disordered regions and functional aspects of experimentally proven host and microbial mimicry proteins.


Asunto(s)
Proteínas Intrínsecamente Desordenadas , Virus , Proteínas Intrínsecamente Desordenadas/química , Péptidos , Dominios Proteicos , Proteínas Virales/metabolismo , Virus/metabolismo
13.
Biol Methods Protoc ; 7(1): bpac031, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36479434

RESUMEN

Antibiotic resistance has escalated as a significant problem of broad public health significance. Regular surveillance of antibiotic resistance genes (ARGs) in microbes and metagenomes from human, animal and environmental sources is vital to understanding ARGs' epidemiology and foreseeing the emergence of new antibiotic resistance determinants. Whole-genome sequencing (WGS)-based identification of the microbial ARGs using antibiotic resistance databases and in silico prediction tools can significantly expedite the monitoring and characterization of ARGs in various niches. The major hindrance to the annotation of ARGs from WGS data is that most genome databases contain fragmented genes/genomes (due to incomplete assembly). Herein, we describe an insilicoBacterial Antibiotic Resistance scan (BacARscan) (http://proteininformatics.org/mkumar/bacarscan/) that can detect, predict and characterize ARGs in -omics datasets, including short sequencing, reads, and fragmented contigs. Benchmarking on an independent non-redundant dataset revealed that the performance of BacARscan was better than other existing methods, with nearly 92% Precision and 95% F-measure on a combined dataset of ARG and non-ARG proteins. One of the most notable improvements of BacARscan over other ARG annotation methods is its ability to work on genomes and short-reads sequence libraries with equal efficiency and without any requirement for assembly of short reads. Thus, BacARscan can help monitor the prevalence and diversity of ARGs in microbial populations and metagenomic samples from animal, human, and environmental settings. The authors intend to constantly update the current version of BacARscan as and when new ARGs are discovered. Executable versions, source codes, sequences used for development and usage instructions are available at (http://www.proteininformatics.org/mkumar/bacarscan/downloads.html) and GitHub repository (https://github.com/mkubiophysics/BacARscan).

14.
Antibiotics (Basel) ; 10(12)2021 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-34943751

RESUMEN

ESKAPE pathogens are the leading cause of nosocomial infections. The Global Priority List of WHO has categorized ESKAPE as priority 1 and 2 pathogens. Even though several mechanisms contribute to antimicrobial resistance, OXA ß-lactamase has emerged as a new threat in combating nosocomial infections. In the present study we have investigated the presence of OXA and their variants, copy number, distribution on chromosomes/plasmids, subfamilies, phylogenetic relationships, amino acid identities and variabilities in ESKAPE pathogens. Our results revealed that a total of 929 OXA were present in 2258 completely assembled genomes, which could be further subdivided into 16 sub-families. Among all the ESKAPE pathogens, OXA were highly prevalent in A. baumannii, followed by P. aeruginosa and K. pneumoniae but completely absent in E. faecium and S. aureus while, only a few copies were found in Enterobacter spp. Most of the OXA variants belonged to the OXA-51-like subfamily (200 proteins), followed by OXA-50-like subfamily (189 proteins), OXA-23-like subfamily (156 proteins) and OXA-1-like subfamily (154 proteins). OXA-51-like, OXA-213-like, OXA-134-like, OXA-58-like, OXA-24-like and OXA-20-like subfamilies were present exclusively in A. baumannii. Phylogenetic tree of the subfamilies revealed that OXA-1-like and OXA-33-like, OXA-51-like and OXA-213-like and, OXA-5-like and OXA-10-like belonged to the same branches with amino acid identities as 100%, 97.10% and 80.90% respectively. This indicates that the members of these subfamily-pairs might have evolved from the same ancestor or have recently diverged. Thus, a judicious use of carbapenems is warranted to curtail the rise of new OXA enzymes and preserve them. This is the first detailed report about the OXA of ESKAPE pathogens.

15.
Infect Genet Evol ; 90: 104767, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33581330

RESUMEN

Escherichia coli is a human commensal and faecal indicator bacteria which is also the etiologic agent of several nosocomial- and community-acquired infections. Amoxicillin-clavulanate (AMC) is a widely prescribed ß-lactam/ß-lactamase inhibitor which is used against E. coli infections. Resistance to AMC in E. coli has been primarily attributed to point mutations in blaTEM-1 resulting in inhibitor-resistant TEM (IRT) ß-lactamases. In this study, we have explored the reasons underlying AMC-resistance in waterborne E. coli. Most of the studies regarding IRT-producing E. coli have been conducted on clinical samples and studies exploring genetic mechanisms underlying AMC-resistance in aquatic E. coli are scarce. Since, blaTEM-1 and several antimicrobial resistance determinants are located on mobile genetic elements they can easily disseminate among other microbes inhabiting urban waterbodies. Thus, it is important to understand the underlying mechanisms to check the dissemination of AMC-resistance in other waterborne pathogens. Our results indicated that AMC-resistant E. coli were susceptible to other ß-lactam/ß-lactamase inhibitors like, ampicillin/sulbactam and piperacillin/tazobactam. Though, blaTEM-1 was present, none of the strains harbored point mutations which could qualify as IRT and only one strain harbored both blaTEM-1 and blaOXA-1. Hyperproduction of blaTEM-1, presence of plasimd-mediated ampC or promoter/attenuator mutations in the chromososmal ampC might not be related to IRT-like phenotype or AMC-resistance. This suggests that other mechanisms like, increased plasmid copy numbers or gene amplification or deficiency in the expression/function of porins might be responsible for AMC-resistance in waterborne E. coli.


Asunto(s)
Combinación Amoxicilina-Clavulanato de Potasio/farmacología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli/genética , Ríos/microbiología , Microbiología del Agua , Inhibidores de beta-Lactamasas/farmacología , Escherichia coli/efectos de los fármacos , India
16.
Front Microbiol ; 12: 621564, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33633708

RESUMEN

Globally, urban water bodies have emerged as an environmental reservoir of antimicrobial resistance (AMR) genes because resistant bacteria residing here might easily disseminate these traits to other waterborne pathogens. In the present study, we have investigated the AMR phenotypes, prevalent plasmid-mediated AMR genes, and integrons in commensal strains of Escherichia coli, the predominant fecal indicator bacteria isolated from a major urban river of northern India Yamuna. The genetic environment of bla CTX-M-15 was also investigated. Our results indicated that 57.5% of the E. coli strains were resistant to at least two antibiotic classes and 20% strains were multidrug resistant, i.e., resistant to three or more antibiotic classes. The multiple antibiotic resistance index of about one-third of the E. coli strains was quite high (>0.2), reflecting high contamination of river Yamuna with antibiotics. With regard to plasmid-mediated AMR genes, bla TEM-1 was present in 95% of the strains, followed by qnrS1 and armA (17% each), bla CTX-M-15 (15%), strA-strB (12%), and tetA (7%). Contrary to the earlier reports where bla CTX-M-15 was mostly associated with pathogenic phylogroup B2, our study revealed that the CTX-M-15 type extended-spectrum ß-lactamases (ESBLs) were present in the commensal phylogroups A and B1, also. The genetic organization of bla CTX-M-15 was similar to that reported for E. coli, isolated from other parts of the world; and ISEcp1 was present upstream of bla CTX-M-15. The integrons of classes 2 and 3 were absent, but class 1 integron gene intI1 was present in 75% of the isolates, denoting its high prevalence in E. coli of river Yamuna. These evidences indicate that due to high prevalence of plasmid-mediated AMR genes and intI1, commensal E. coli can become vehicles for widespread dissemination of AMR in the environment. Thus, regular surveillance and management of urban rivers is necessary to curtail the spread of AMR and associated health risks.

17.
PLoS One ; 16(8): e0255826, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34358261

RESUMEN

Secretory proteins are important for microbial adaptation and survival in a particular environment. Till date, experimental secretomes have been reported for a few archaea. In this study, we have identified the experimental secretome of Picrophilous torridus and evaluated the efficacy of various signal peptide predictors (SPPs) in identifying signal peptides (SPs) in its experimental secretome. Liquid chromatography mass spectrometric (LC MS) analysis was performed for three independent P. torridus secretome samples and only those proteins which were common in the three experiments were selected for further analysis. Thus, 30 proteins were finally included in this study. Of these, 10 proteins were identified as hypothetical/uncharacterized proteins. Gene Ontology, KEGG and STRING analyses revealed that majority of the sercreted proteins and/or their interacting partners were involved in different metabolic pathways. Also, a few proteins like malate dehydrogenase (Q6L0C3) were multi-functional involved in different metabolic pathways like carbon metabolism, microbial metabolism in diverse environments, biosynthesis of antibiotics, etc. Multi-functionality of the secreted proteins reflects an important aspect of thermoacidophilic adaptation of P. torridus which has the smallest genome (1.5 Mbp) among nonparasitic aerobic microbes. SPPs like, PRED-SIGNAL, SignalP 5.0, PRED-TAT and LipoP 1.0 identified SPs in only a few secreted proteins. This suggests that either these SPPs were insufficient, or N-terminal SPs were absent in majority of the secreted proteins, or there might be alternative mechanisms of protein translocation in P. torridus.


Asunto(s)
Archaea , Cromatografía Liquida , Señales de Clasificación de Proteína , Proteoma
18.
Sci Rep ; 11(1): 15288, 2021 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-34315963

RESUMEN

Lactobacillus plantarum (renamed as Lactiplantibacillus plantarum) has been isolated from many sources but very rarely from rhizospheric soil. This is the first report on isolation and assessment of probiotic capabilities of L. plantarum strains isolated from rhizospheric soil. The isolates were confirmed by 16S rRNA gene sequencing and named as NS14, NS16 and NGG. All the isolates were evaluated for bile salt hydrolysis, hypocholestrolemic potential and probiotic attributes. Our results indicated that all the strains harboured bsh and showed in vitro cholesterol assimilation capabilities which increased when bile salts were also present in the culture medium. Also, all the strains remained viable at high temperatures and in the presence of NaCl, lysozyme, simulated gastric juice, bile salts and, exhibited auto- and co-aggregation capabilities. Additionally, L. plantarum strain NS14 survived in the presence of phenols, acidic environment (pH 2-3) and was resistant to many clinically relevant antibiotics. Since, L. plantarum NS14 exhibited most of the desirable and essential characteristics of a probiotic it should be further investigated as a potent probiotic with an additional benefit as a hypocholesterolemic biotherapeutic. Moreover, rhizosphere can be explored as a useful ecological niche for isolating microorganisms with biotechnological and probiotic potential.


Asunto(s)
Anticolesterolemiantes/farmacología , Ácidos y Sales Biliares/metabolismo , Lactobacillus plantarum/metabolismo , Probióticos , Secuencia de Aminoácidos , Hidrólisis , Técnicas In Vitro , Lactobacillus plantarum/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Homología de Secuencia de Aminoácido
19.
Protein Pept Lett ; 28(6): 675-679, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33243110

RESUMEN

BACKGROUND: CsaA is among the few chaperones which are present in both bacteria and archaea, but absent in eukaryotes. There are no reports on interactome analysis of CsaA from archaea, till date. Identification of binding partners of CsaA might be helpful in understanding CsaA-associated processes in Picrophilus torridus an extreme thermoacidophilic euryarchaeon. OBJECTIVES: The present study was conducted to identify the binding partners of CsaA of P. torridus (PtCsaA). METHODS: The binding partners of PtCsaA were isolated and identified using a pull down assay and liquid chromatography-mass spectrometry (LC-MS). RESULTS: The results revealed twelve potential binding partners of CsaA. These were thermosome subunits (Q6KZS2 and Q6L132), nascent polypeptide-associated complex protein (Q6L1N3), elongation factor 1-alpha (Q6L202), uncharacterized protein (Q6L0Y6), citrate synthase (Q6L0M8), asparaginyl- tRNA synthetase (Q6L0M5), succinyl-CoA synthetase beta chain (Q6L0B4), pyruvate ferredoxin oxidoreductase alpha and beta chain proteins (Q6KZA7 and Q6KZA6, respectively), malate dehydrogenase (Q6L0C3) and reversed fumarylacetoacetase (Q6KZ97). Functional categorization revealed that of these, six proteins were involved in energy metabolic pathways, three were archaeal chaperones, two were involved in translation and one might be a transcription regulator. STRING-based analysis of the protein-protein interactions of the experimental interactome revealed strong interactions among them. CONCLUSION: PtCsaA might be a multifaceted protein which besides translation might also play important role in metabolic processes of P. torridus. However, further experiments investigating the binding partners of CsaA in other archaea are required for a better understanding of CsaA-associated processes in archaea.


Asunto(s)
Proteínas Bacterianas , Chaperonas Moleculares , Thermoplasmales/química , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Cromatografía Liquida , Espectrometría de Masas , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Unión Proteica , Mapas de Interacción de Proteínas
20.
Proteome Sci ; 8: 59, 2010 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-21083941

RESUMEN

BACKGROUND: Streptomycin (SM) is a broad spectrum antibiotic and is an important component of any anti-tuberculosis therapy regimen. Several mechanisms have been proposed to explain the emergence of resistance but still our knowledge is inadequate. Proteins form a very complex network and drugs are countered by their modification/efflux or over expression/modification of targets. As proteins manifest most of the biological processes, these are attractive targets for developing drugs, immunodiagnostics or therapeutics. The aim of present study was to analyze and compare the protein profile of whole cell extracts from Mycobacterium tuberculosis clinical isolates susceptible and resistant to SM. RESULTS: Two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was employed for analyzing the protein profiles. Homology and in silico characterization for identified proteins was assessed using BLAST, InterProScan and KEGG database searches. Computational studies on the possible interactions between SM and identified proteins were carried out by a battery of online servers and softwares, namely, CLUSTALW (KEGG), I-TASSER, VMD, PatchDock and FireDock. On comparing 2DE patterns, nine proteins were found consistently overexpressed in SM resistant isolates and were identified as Rv0350, Rv0440, Rv1240, Rv3075c, Rv2971, Rv3028c, Rv2145c, Rv2031c and Rv0569. In silico docking analysis showed significant interactions of SM with essential (Rv0350, Rv0440 and Rv2971) and non essential (Rv1240, Rv3075c and Rv2031c) genes. CONCLUSIONS: The computational results suggest high protein binding affinity of SM and suggested many possible interactions between identified proteins and the drug. Bioinformatic analysis proves attributive for analysis of diversity of proteins identified by whole proteome analysis. In-depth study of the these proteins will give an insight into probable sites of drug action other than established primary sites and hence may help in search of novel chemotherapeutic agents at these new sites as inhibitors.

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