Premature Termination of MexR Leads to Overexpression of MexAB-OprM Efflux Pump in Pseudomonas aeruginosa in a Tertiary Referral Hospital in India.
OBJECTIVES:The present study was undertaken to investigate the mutations that are present in mexR gene of multidrug resistant (MDR) isolates of Pseudomonas aeruginosa collected from a tertiary referral hospital of north east India. METHODS:76 MDR clinical isolates of P. aeruginosa were obtained from...
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Public Library of Science (PLoS)
2016-01-01
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| Online Access: | http://europepmc.org/articles/PMC4750933?pdf=render |
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| author | Debarati Choudhury Anamika Ghose Debadatta Dhar Chanda Anupam Das Talukdar Manabendra Dutta Choudhury Deepjyoti Paul Anand Prakash Maurya Atanu Chakravarty Amitabha Bhattacharjee |
| author_facet | Debarati Choudhury Anamika Ghose Debadatta Dhar Chanda Anupam Das Talukdar Manabendra Dutta Choudhury Deepjyoti Paul Anand Prakash Maurya Atanu Chakravarty Amitabha Bhattacharjee |
| author_sort | Debarati Choudhury |
| collection | DOAJ |
| description | OBJECTIVES:The present study was undertaken to investigate the mutations that are present in mexR gene of multidrug resistant (MDR) isolates of Pseudomonas aeruginosa collected from a tertiary referral hospital of north east India. METHODS:76 MDR clinical isolates of P. aeruginosa were obtained from the patients who were admitted to or attended the clinics of Silchar medical college and hospital. They were screened phenotypically for the presence of efflux pump activity by an inhibitor based method. Acquired resistance mechanisms were detected by multiplex PCR. Real time PCR was performed to study the expression of mexA gene of MexAB-OprM efflux pump in isolates with increase efflux pump activity. mexR gene of the isolates with overexpressed MexAB-OprM efflux pump was amplified, sequenced and analysed. RESULTS:Out of 76 MDR isolates, 24 were found to exhibit efflux pump activity phenotypically against ciprofloxacin and meropenem. Acquired resistance mechanisms were absent in 11 of them and among those isolates, 8 of them overexpressed MexAB-OprM. All the 8 isolates possessed mutation in mexR gene. 11 transversions, 4 transitions, 2 deletion mutations and 2 insertion mutations were found in all the isolates. However, the most significant observation was the formation of a termination codon at 35th position which resulted in the termination of the polypeptide and leads to overexpression of the MexAB-OprM efflux pump. CONCLUSIONS:This study highlighted emergence of a novel mutation which is probably associated with multi drug resistance. Therefore, further investigations and actions are needed to prevent or at least hold back the expansion and emergence of newer mutations in nosocomial pathogens which may compromise future treatment options. |
| first_indexed | 2024-12-10T15:33:17Z |
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| language | English |
| last_indexed | 2024-12-10T15:33:17Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-e40c7305654c4b598c7782107d4b0b272022-12-22T01:43:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014915610.1371/journal.pone.0149156Premature Termination of MexR Leads to Overexpression of MexAB-OprM Efflux Pump in Pseudomonas aeruginosa in a Tertiary Referral Hospital in India.Debarati ChoudhuryAnamika GhoseDebadatta Dhar ChandaAnupam Das TalukdarManabendra Dutta ChoudhuryDeepjyoti PaulAnand Prakash MauryaAtanu ChakravartyAmitabha BhattacharjeeOBJECTIVES:The present study was undertaken to investigate the mutations that are present in mexR gene of multidrug resistant (MDR) isolates of Pseudomonas aeruginosa collected from a tertiary referral hospital of north east India. METHODS:76 MDR clinical isolates of P. aeruginosa were obtained from the patients who were admitted to or attended the clinics of Silchar medical college and hospital. They were screened phenotypically for the presence of efflux pump activity by an inhibitor based method. Acquired resistance mechanisms were detected by multiplex PCR. Real time PCR was performed to study the expression of mexA gene of MexAB-OprM efflux pump in isolates with increase efflux pump activity. mexR gene of the isolates with overexpressed MexAB-OprM efflux pump was amplified, sequenced and analysed. RESULTS:Out of 76 MDR isolates, 24 were found to exhibit efflux pump activity phenotypically against ciprofloxacin and meropenem. Acquired resistance mechanisms were absent in 11 of them and among those isolates, 8 of them overexpressed MexAB-OprM. All the 8 isolates possessed mutation in mexR gene. 11 transversions, 4 transitions, 2 deletion mutations and 2 insertion mutations were found in all the isolates. However, the most significant observation was the formation of a termination codon at 35th position which resulted in the termination of the polypeptide and leads to overexpression of the MexAB-OprM efflux pump. CONCLUSIONS:This study highlighted emergence of a novel mutation which is probably associated with multi drug resistance. Therefore, further investigations and actions are needed to prevent or at least hold back the expansion and emergence of newer mutations in nosocomial pathogens which may compromise future treatment options.http://europepmc.org/articles/PMC4750933?pdf=render |
| spellingShingle | Debarati Choudhury Anamika Ghose Debadatta Dhar Chanda Anupam Das Talukdar Manabendra Dutta Choudhury Deepjyoti Paul Anand Prakash Maurya Atanu Chakravarty Amitabha Bhattacharjee Premature Termination of MexR Leads to Overexpression of MexAB-OprM Efflux Pump in Pseudomonas aeruginosa in a Tertiary Referral Hospital in India. PLoS ONE |
| title | Premature Termination of MexR Leads to Overexpression of MexAB-OprM Efflux Pump in Pseudomonas aeruginosa in a Tertiary Referral Hospital in India. |
| title_full | Premature Termination of MexR Leads to Overexpression of MexAB-OprM Efflux Pump in Pseudomonas aeruginosa in a Tertiary Referral Hospital in India. |
| title_fullStr | Premature Termination of MexR Leads to Overexpression of MexAB-OprM Efflux Pump in Pseudomonas aeruginosa in a Tertiary Referral Hospital in India. |
| title_full_unstemmed | Premature Termination of MexR Leads to Overexpression of MexAB-OprM Efflux Pump in Pseudomonas aeruginosa in a Tertiary Referral Hospital in India. |
| title_short | Premature Termination of MexR Leads to Overexpression of MexAB-OprM Efflux Pump in Pseudomonas aeruginosa in a Tertiary Referral Hospital in India. |
| title_sort | premature termination of mexr leads to overexpression of mexab oprm efflux pump in pseudomonas aeruginosa in a tertiary referral hospital in india |
| url | http://europepmc.org/articles/PMC4750933?pdf=render |
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