{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:43:32Z","timestamp":1792597412208,"version":"4.5.0"},"reference-count":108,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\u03b2-lactam resistance represents a worldwide problem and a serious challenge for antimicrobial treatment. Hence this research was conducted to recognize several mechanisms mediating \u03b2-lactam resistance in <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> and <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> clinical isolates collected from Mansoura University hospitals, Egypt. A total of 80 isolates, 45 <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> and 35 <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> isolates, were collected and their antibiotic susceptibility was determined by the Disc diffusion method followed by phenotypic and genotypic detection of extended-spectrum \u03b2-lactamases (ESBLs), AmpC \u03b2-lactamase, carbapenemase enzymes. The outer membrane protein porins of all isolates were analyzed and their genes were examined using gene amplification and sequencing. Also, the resistance to complement-mediated serum killing was estimated. A significant percentage of isolates (93.8%) were multidrug resistance and showed an elevated resistance to \u03b2-lactam antibiotics. The presence of either ESBL or AmpC enzymes was high among isolates (83.75%). Also, 60% of the isolated strains were carbapenemase producers. The most frequently detected gene of ESBL among all tested isolates was <jats:italic>bla<\/jats:italic><jats:sub>CTX-M-15<\/jats:sub> (86.3%) followed by <jats:italic>bla<\/jats:italic><jats:sub>TEM-1<\/jats:sub> (81.3%) and <jats:italic>bla<\/jats:italic><jats:sub>SHV-1<\/jats:sub> (35%) while <jats:italic>the Amp-<\/jats:italic>C gene was present in 83.75%. For carbapenemase-producing isolates, <jats:italic>bla<\/jats:italic><jats:sub>NDM1<\/jats:sub> was the most common (60%) followed by <jats:italic>bla<\/jats:italic><jats:sub>VIM-1<\/jats:sub> (35%) and <jats:italic>bla<\/jats:italic><jats:sub>OXA-48<\/jats:sub> (13.8%). Besides, 73.3% and 40% of <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> and <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> isolates respectively were serum resistant. Outer membrane protein analysis showed that 93.3% of <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> and 95.7% of <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> isolates lost their porins or showed modified porins. Furthermore, sequence analysis of tested porin genes in some isolates revealed the presence of frameshift mutations that produced truncated proteins of smaller size. \u03b2-lactam resistance in <jats:italic>K<\/jats:italic>. <jats:italic>pneumoniae<\/jats:italic> and <jats:italic>E<\/jats:italic>. <jats:italic>coli<\/jats:italic> isolates in our hospitals is due to a combination of \u03b2-lactamase activity and porin loss\/alteration. Hence more restrictions should be applied on \u03b2-lactams usage to decrease the emergence of resistant strains.<\/jats:p>","DOI":"10.1371\/journal.pone.0251594","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T17:43:36Z","timestamp":1621532616000},"page":"e0251594","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":82,"title":["\u03b2-lactam resistance associated with \u03b2-lactamase production and porin alteration in clinical isolates of E. coli and K. pneumoniae"],"prefix":"10.1371","volume":"16","author":[{"given":"Sara M.","family":"Khalifa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6214-5091","authenticated-orcid":true,"given":"Abeer M.","family":"Abd El-Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramadan","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman S.","family":"Abdelmegeed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,5,20]]},"reference":[{"key":"pone.0251594.ref001","volume-title":"Antimicrobial resistance: global report on surveillance","author":"Health Organization (WHO)","year":"2014"},{"key":"pone.0251594.ref002","article-title":"ASM task force urges a broad program of antimicrobial resistance","volume":"61","author":"H Cassell Gail","year":"1995","journal-title":"ASM News"},{"issue":"5157","key":"pone.0251594.ref003","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1126\/science.8153625","article-title":"Prevention of drug access to bacterial targets: permeability barriers and active efflux","volume":"264","author":"H Nikaido","year":"1994","journal-title":"Science"},{"issue":"5157","key":"pone.0251594.ref004","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1126\/science.8153626","article-title":"Resistance to antibiotics mediated by target alterations","volume":"264","author":"BG Spratt","year":"1994","journal-title":"Science"},{"issue":"6","key":"pone.0251594.ref005","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1128\/AAC.35.6.1174","article-title":"Imipenem-and meropenem-resistant mutants of Enterobacter cloacae and Proteus Rettgeri lack porins","volume":"35","author":"A Raimondi","year":"1991","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"2","key":"pone.0251594.ref006","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1128\/AAC.39.2.350","article-title":"Relative importance of outer membrane permeability and group 1 beta-lactamase as determinants of meropenem and imipenem activities against Enterobacter cloacae","volume":"39","author":"G Cornaglia","year":"1995","journal-title":"Antimicrobial agents and chemotherapy"},{"key":"pone.0251594.ref007","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/nyas.12537","article-title":"Carbapenem-resistant Enterobacteriaceae: biology, epidemiology, and management","volume":"1323","author":"E Temkin","year":"2014","journal-title":"Ann. 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