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Khan, Faisal Ahmad
Publications (10 of 10) Show all publications
Khan, F. A. (2020). Carbapenemase-Producing Enterobacteriaceae in Wastewater-Associated Aquatic Environments. (Doctoral dissertation). Örebro: Örebro University
Open this publication in new window or tab >>Carbapenemase-Producing Enterobacteriaceae in Wastewater-Associated Aquatic Environments
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The emergence of carbapenem resistance due to the carbapenem-hydrolyzing enzymes (carbapenemases) in Enterobacteriaceae has led to limited therapeutic options. The increased resistance to these “last-resort” antibiotics is fueled by overuse and misuse of antibiotics in human medicine and agriculture. According to the One-Health concept, the microbiomes of humans, animals and natural environments are interconnected reservoirs of antibiotic resistance genes (ARGs) and changes in one compartment will affect the other compartments. Thus, the environmental waters exposed to the pathogens, ARGs and other contaminants of human origin can play a significant role in the spread of resistance. The study aimed to characterize carbapenemase-producing Enterobacteriaceae (CPE) and ARGs in wastewaters and associated river and lake waters in Örebro, Sweden. The study also analyzed de novo development of resistance in Klebsiella oxytoca during long-term growth in river water and the effect of temperature on the emergence of resistance. OXA-48-producing Escherichia coli (ST131) and VIM-1-producing K.oxytoca (ST172) were repeatedly detected in the wastewaters and associated river, suggesting that these isolates were persistently present in these environments. Furthermore, K. oxytoca ST172 isolated from the river was genetically similar to two isolates previously recovered from patients in a local hospital, which shows the possibility of transmission of CPE from hospital to aquatic environments. A high diversity of ARGs was detected in these environments especially in hospital wastewater where ten different carbapenemase genes were detected. These results emphasized that the effective treatment of wastewaters must be ensured to reduce or eliminate the spread of antibiotic resistance. Increased resistance to meropenem (up to 8-fold) and ceftazidime (>10-fold) was observed in K. oxytoca after exposure to both river and tap water after 600 generations and resistance emerged earlier when the bacteria was grown at the higher temperature. The exposure to contaminants and increased environmental temperature may induce similar changes in the environmental microbiome, generating novel resistant variants at accelerated rates that may pose a significant threat to human health.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2020. p. 81
Series
Örebro Studies in Life Science ; 16
Keywords
Antibiotic resistance evolution, ESBL, Klebsiella, Multidrug, VIM
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-81150 (URN)978-91-7529-334-9 (ISBN)
Public defence
2020-06-08, Örebro universitet, Forumhuset, Hörsal F, Fakultetsgatan 1, Örebro, 10:00 (Swedish)
Opponent
Supervisors
Available from: 2020-04-15 Created: 2020-04-15 Last updated: 2020-05-13Bibliographically approved
Fagerström, A., Mölling, P., Khan, F. A., Sundqvist, M., Jass, J. & Söderquist, B. (2019). Comparative distribution of extended-spectrum beta-lactamase-producing Escherichia coli from urine infections and environmental waters. PLoS ONE, 14(11), Article ID e0224861.
Open this publication in new window or tab >>Comparative distribution of extended-spectrum beta-lactamase-producing Escherichia coli from urine infections and environmental waters
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2019 (English)In: PLoS ONE, E-ISSN 1932-6203, Vol. 14, no 11, article id e0224861Article in journal (Refereed) Published
Abstract [en]

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have been reported in natural environments, and may be released through wastewater. In this study, the genetic relationship between ESBL-producing E. coli collected from patient urine samples (n = 45, both hospitalized patients and out-patients) and from environmental water (n = 82, from five locations), during the same time period, was investigated. Three independent water samples were collected from the municipal wastewater treatment plant, both incoming water and treated effluent water; the receiving river and lake; and a bird sanctuary near the lake, on two different occasions. The water was filtered and cultured on selective chromID ESBL agar plates in order to detect and isolate ESBL-producing E. coli. Illumina whole genome sequencing was performed on all bacterial isolates (n = 127). Phylogenetic group B2 was more common among the clinical isolates than the environmental isolates (44.4% vs. 17.1%, p < 0.01) due to a significantly higher prevalence of sequence type (ST) 131 (33.3% vs. 13.4%, p < 0.01). ST131 was, however, one of the most prevalent STs among the environmental isolates. There was no significant difference in diversity between the clinical isolates (DI 0.872 (0.790-0.953)) and the environmental isolates (DI 0.947 (0.920-0.969)). The distribution of ESBL genes was similar: blaCTX-M-15 dominated, followed by blaCTX-M-14 and blaCTX-M-27 in both the clinical (60.0%, 8.9%, and 6.7%) and the environmental isolates (62.2%, 12.2%, and 8.5%). Core genome multi-locus sequence typing showed that five environmental isolates, from incoming wastewater, treated wastewater, Svartån river and Hjälmaren lake, were indistinguishable or closely related (≤10 allele differences) to clinical isolates. Isolates of ST131, serotype O25:H4 and fimtype H30, from the environment were as closely related to the clinical isolates as the isolates from different patients were. This study confirms that ESBL-producing E. coli are common in the aquatic environment even in low-endemic regions and suggests that wastewater discharge is an important route for the release of ESBL-producing E. coli into the aquatic environment.

Place, publisher, year, edition, pages
PLOS, 2019
National Category
Microbiology
Identifiers
urn:nbn:se:oru:diva-77879 (URN)10.1371/journal.pone.0224861 (DOI)000532694400072 ()31697734 (PubMedID)2-s2.0-85074687903 (Scopus ID)
Funder
Swedish Research Council Formas, 2192014-837
Note

Funding Agency:

Research committee of Region Örebro County  OLL-406511 OLL-367741 OLL-748091

Available from: 2019-11-14 Created: 2019-11-14 Last updated: 2020-05-29Bibliographically approved
Yewale, P. P., Lokhande, K. B., Sridhar, A., Vaishnav, M., Khan, F. A., Mandal, A., . . . Nawani, N. (2019). Molecular profiling of multidrug-resistant river water isolates: insights into resistance mechanism and potential inhibitors. Environmental science and pollution research international
Open this publication in new window or tab >>Molecular profiling of multidrug-resistant river water isolates: insights into resistance mechanism and potential inhibitors
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2019 (English)In: Environmental science and pollution research international, ISSN 0944-1344, E-ISSN 1614-7499Article in journal (Refereed) Epub ahead of print
Abstract [en]

Polluted waters are an important reservoir for antibiotic resistance genes and multidrug-resistant bacteria. This report describes the microbial community, antibiotic resistance genes, and the genetic profile of extended spectrum β-lactamase strains isolated from rivers at, Pune, India. ESBL-producing bacteria isolated from diverse river water catchments running through Pune City were characterized for their antibiotic resistance. The microbial community and types of genes which confer antibiotic resistance were identified followed by the isolation of antibiotic-resistant bacteria on selective media and their genome analysis. Four representative isolates were sequenced using next generation sequencing for genomic analysis. They were identified as Pseudomonas aeruginosa, Escherichia coli, and two isolates were Enterobacter cloacae. The genes associated with the multidrug efflux pumps, such as tolC, macA, macB, adeL, and rosB, were detected in the isolates. As MacAB-TolC is an ABC type efflux pump responsible for conferring resistance in bacteria to several antibiotics, potential efflux pump inhibitors were identified by molecular docking. The homology model of their MacB protein with that from Escherichia coli K12 demonstrated structural changes in different motifs of MacB. Molecular docking of reported efflux pump inhibitors revealed the highest binding affinity of compound MC207-110 against MacB. It also details the potential efflux pump inhibitors that can serve as possible drug targets in drug development and discovery.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Antimicrobial resistance, Efflux pump inhibitors, Extended spectrum β-lactamase, MacB, Multidrug efflux pump
National Category
Microbiology
Identifiers
urn:nbn:se:oru:diva-75620 (URN)10.1007/s11356-019-05738-2 (DOI)31236860 (PubMedID)
Available from: 2019-08-20 Created: 2019-08-20 Last updated: 2019-08-20Bibliographically approved
Khan, F. A., Söderquist, B. & Jass, J. (2019). Prevalence and Diversity of Antibiotic Resistance Genes in Swedish Aquatic Environments Impacted by Household and Hospital Wastewater. Frontiers in Microbiology, 10, Article ID 688.
Open this publication in new window or tab >>Prevalence and Diversity of Antibiotic Resistance Genes in Swedish Aquatic Environments Impacted by Household and Hospital Wastewater
2019 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, article id 688Article in journal (Refereed) Published
Abstract [en]

Antibiotic-resistant Enterobacteriaceae and non-lactose fermenting Gram-negative bacteria are a major cause of nosocomial infections. Antibiotic misuse has fueled the worldwide spread of resistant bacteria and the genes responsible for antibiotic resistance (ARGs). There is evidence that ARGs are ubiquitous in non-clinical environments, especially those affected by anthropogenic activity. However, the emergence and primary sources of ARGs in the environment of countries with strict regulations for antibiotics usage are not fully explored. The aim of the present study was to evaluate the repertoire of ARGs of culturable Gram-negative bacteria from directionally connected sites from the hospital to the wastewater treatment plant (WWTP), and downstream aquatic environments in central Sweden. The ARGs were detected from genomic DNA isolated from a population of selectively cultured coliform and Gram-negative bacteria using qPCR. The results show that hospital wastewater was a reservoir of several class B beta-lactamase genes such as bla(IMP)(-1), bla(IMP)(-2), and bla(OXA-23), however, most of these genes were not observed in downstream locations. Moreover, beta-lactamase genes such as bla(OXA-48), bla(CDX-M-8), and bla(SFC-1), bla(VIM-1), and bla(VIM-13) were detected in downstream river water but not in the WWTP. The results indicate that the WWTP and hospital wastewaters were reservoirs of most ARGs and contribute to the diversity of ARGs in associated natural environments. However, this study suggests that other factors may also have minor contributions to the prevalence and diversity of ARGs in natural environments.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
carbapenemase, urban wastewater, surface water, enterobacteriaceae, VIM-1, extended-spectrum beta-lactamase, antimicrobial resistance gene co-occurrence
National Category
Microbiology
Identifiers
urn:nbn:se:oru:diva-73758 (URN)10.3389/fmicb.2019.00688 (DOI)000463403600001 ()
Funder
Swedish Research Council Formas, 219-2014-837Knowledge Foundation, 20150084
Note

Funding Agencies:

Nyckelfonden at Örebro University Hospital  

Örebro University 

Available from: 2019-04-16 Created: 2019-04-16 Last updated: 2020-05-13Bibliographically approved
Goswami, M., Khan, F. A., Ibrisevic, A., Olsson, P.-E. & Jass, J. (2018). Development of Escherichia coli-based gene expression profiling of sewage sludge leachates. Journal of Applied Microbiology, 125(5), 1502-1517
Open this publication in new window or tab >>Development of Escherichia coli-based gene expression profiling of sewage sludge leachates
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2018 (English)In: Journal of Applied Microbiology, ISSN 1364-5072, E-ISSN 1365-2672, Vol. 125, no 5, p. 1502-1517Article in journal (Refereed) Published
Abstract [en]

AIMS: The impact of municipal waste on pathogenic microorganisms released into the environment is a public health concern. The present study aims to evaluate the effects of sewage sludge and antibiotic contaminants on stress response, virulence and antibiotic resistance in a pathogenic Escherichia coli.

METHODS AND RESULTS: The effects of sewage sludge leachates on uropathogenic E. coli CFT073 were determined by monitoring the expression of 45 genes associated with antibiotic/metal resistance, stress response and virulence using RT-qPCR. The E. coli gene expression was validated using sub-inhibitory concentrations of tetracycline and ciprofloxacin. E. coli exposed to sewage sludge or sewage sludge-fly ash leachates altered the expression of 5 antibiotic and metal resistance, 3 stress response and 2 virulence associated genes. When antibiotics were combined with sludge or sludge-fly ash the antibiotic-associated gene expression was altered.

CONCLUSIONS: E. coli treated with two sludge leachates had distinct gene expression patterns that were altered when the sludge leachates were combined with tetracycline, although to a lesser extent with ciprofloxacin.

SIGNIFICANCE AND IMPACT OF STUDY: The E. coli multigene expression analysis is a potential new tool for assessing the effects of pollutants on pathogenic microbes in environmental waters for improved risk assessment.

Place, publisher, year, edition, pages
Blackwell Publishing, 2018
Keywords
Ecotoxicity, Gene expression, Resistance, Sludge, Stress response, Virulence
National Category
Microbiology
Identifiers
urn:nbn:se:oru:diva-67511 (URN)10.1111/jam.14028 (DOI)000447408400024 ()29928772 (PubMedID)2-s2.0-85050482911 (Scopus ID)
Funder
Knowledge Foundation, Dnr 20110177
Available from: 2018-06-26 Created: 2018-06-26 Last updated: 2018-11-01Bibliographically approved
Khan, F. A., Hellmark, B., Ehricht, R., Söderquist, B. & Jass, J. (2018). Related carbapenemase-producing Klebsiella isolates detected in both a hospital and associated aquatic environment in Sweden. European Journal of Clinical Microbiology and Infectious Diseases, 37(12), 2241-2251
Open this publication in new window or tab >>Related carbapenemase-producing Klebsiella isolates detected in both a hospital and associated aquatic environment in Sweden
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2018 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 37, no 12, p. 2241-2251Article in journal (Refereed) Published
Abstract [en]

Carbapenem antibiotics are one of the last-resort agents against multidrug-resistant (MDR) bacteria. The occurrence of carbapenemase-producing Enterobacteriaceae (CPE) in wastewater and aquatic environments is an indication of MDR bacteria in the community. This study evaluated CPE in aquatic environments and compared them to the local hospital isolates in Sweden. Phenotypic and genotypic analyses of antibiotic resistance of environmental and clinical CPE were performed. The relatedness of the isolates and possible clonal dissemination was evaluated using phylogenetic and phyloproteomic analysis. Klebsiella oxytoca carrying carbapenemase genes (blaVIM-1, blaIMP-29) were isolated from wastewater and the recipient river, while K. oxytoca (blaVIM-1) and Klebsiella pneumoniae (blaVIM-1, blaOXA-48, blaNDM-1, blaKPC-3) were isolated from patients at the local clinics or hospital. The K. oxytoca classified as sequence type 172 (ST172) isolated from the river was genotypically related to two clinical isolates recovered from patients. The similarity between environmental and clinical isolates suggests the dispersion of blaVIM-1 producing K. oxytoca ST172 from hospital to aquatic environment and the likelihood of its presence in the community. This is the first report of CPE in aquatic environments in Sweden; therefore, surveillance of aquatic and hospital environments for CPE in other urban areas is important to determine the major transfer routes in order to formulate strategies to prevent the spread of MDR bacteria.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Antimicrobial resistance, Carbapenemase-producing Enterobacteriaceae, Extended spectrum beta-lactamase, Klebsiella oxytoca, Klebsiella pneumoniae, Multidrug resistance
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-68676 (URN)10.1007/s10096-018-3365-9 (DOI)000449921100003 ()30171482 (PubMedID)2-s2.0-85053311566 (Scopus ID)
Funder
Swedish Research Council Formas, 219-2014-837
Note

Funding Agency:

Nyckelfonden at Orebro University Hospital 

Available from: 2018-09-03 Created: 2018-09-03 Last updated: 2020-05-13Bibliographically approved
Kumar, R., Pradhan, A., Khan, F. A., Lindström, P., Ragnvaldsson, D., Ivarsson, P., . . . Jass, J. (2015). Comparative analysis of stress induced gene expression in caenorhabditis elegans following exposure to environmental and lab reconstituted complex metal mixture. PLoS ONE, 10(7), Article ID e0132896.
Open this publication in new window or tab >>Comparative analysis of stress induced gene expression in caenorhabditis elegans following exposure to environmental and lab reconstituted complex metal mixture
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, article id e0132896Article in journal (Refereed) Published
Abstract [en]

Metals are essential for many physiological processes and are ubiquitously present in the environment. However, high metal concentrations can be harmful to organisms and lead to physiological stress and diseases. The accumulation of transition metals in the environment due to either natural processes or anthropogenic activities such as mining results in the contamination of water and soil environments. The present study used Caenorhabditis elegans to evaluate gene expression as an indicator of physiological response, following exposure to water collected from three different locations downstream of a Swedish mining site and a lab reconstituted metal mixture. Our results indicated that the reconstituted metal mixture exerted a direct stress response in C. elegans whereas the environmental waters elicited either a diminished or abrogated response. This suggests that it is not sufficient to use the biological effects observed from laboratory mixtures to extrapolate the effects observed in complex aquatic environments and apply this to risk assessment and intervention.

National Category
Environmental Sciences
Research subject
Enviromental Science
Identifiers
urn:nbn:se:oru:diva-45584 (URN)10.1371/journal.pone.0132896 (DOI)000358193100095 ()26168046 (PubMedID)
Funder
Knowledge Foundation, 20110183
Note

Funding Agencies:

Örebro Universitet J62200

Boliden Mineral AB

Envix Nord AB

ALS Scandinavia AB

Available from: 2015-08-18 Created: 2015-08-18 Last updated: 2017-12-04Bibliographically approved
Khan, F. A., Rahman, A., Söderquist, B. & Jass, J.Carbapenemase-producing Escherichia coli ST38 and Klebsiella oxytoca ST172 are persistent in Swedish wastewaters and associated river.
Open this publication in new window or tab >>Carbapenemase-producing Escherichia coli ST38 and Klebsiella oxytoca ST172 are persistent in Swedish wastewaters and associated river
(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-81831 (URN)
Available from: 2020-05-13 Created: 2020-05-13 Last updated: 2020-05-13Bibliographically approved
Rahman, A., Khan, F. A., Söderquist, B., Nawani, N. & Jass, J.Diversity of Antibiotic Resistance Genes in Aquatic Environments Using Culture-Dependent and Independent Methods.
Open this publication in new window or tab >>Diversity of Antibiotic Resistance Genes in Aquatic Environments Using Culture-Dependent and Independent Methods
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(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-81832 (URN)
Available from: 2020-05-13 Created: 2020-05-13 Last updated: 2020-05-13Bibliographically approved
Khan, F. A., Rahman, A., Hughes, D., Söderquist, B. & Jass, J.Environmental Conditions Promote Genetic Changes and Increase Resistance to β-lactam Antibiotics in Klebsiella oxytoca.
Open this publication in new window or tab >>Environmental Conditions Promote Genetic Changes and Increase Resistance to β-lactam Antibiotics in Klebsiella oxytoca
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(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Identifiers
urn:nbn:se:oru:diva-81833 (URN)
Available from: 2020-05-13 Created: 2020-05-13 Last updated: 2020-05-13Bibliographically approved
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