{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:11:32Z","timestamp":1791342692319,"version":"4.3.1"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,8,28]]},"abstract":"\n Heteroresistance to \u03b2-lactam antibiotics has been mainly described for staphylococci, for which it complicates diagnostic procedures and therapeutic success. This study investigated whether heteroresistance to penicillin exists in\n Streptococcus pneumoniae<\/jats:italic>\n . Population analysis profile (PAP) showed the presence of subpopulations with higher penicillin resistance in four of nine clinical pneumococcal strains obtained from a local surveillance program (representing the multiresistant clones ST179, ST276, and ST344) and in seven of 16 reference strains (representing the international clones Spain\n 23F<\/jats:sup>\n -1, Spain\n 9V<\/jats:sup>\n -3, Spain\n 14<\/jats:sup>\n -5, Hungary\n 19A<\/jats:sup>\n -6, South Africa\n 19A<\/jats:sup>\n -13, Taiwan\n 23F<\/jats:sup>\n -15, and Finland\n 6B<\/jats:sup>\n -12). Heteroresistant strains had penicillin minimal inhibitory concentrations (MICs) (for the majority of cells) in the intermediate- to high-level range (0.19\u20132.0 \u03bcg\/ml). PAP curves suggested the presence of subpopulations also for the highly penicillin-resistant strains Taiwan\n 19F<\/jats:sup>\n -14, Poland\n 23F<\/jats:sup>\n -16, CSR\n 19A<\/jats:sup>\n -11, and CSR\n 14<\/jats:sup>\n -10. PAP of bacterial subpopulations with higher penicillin resistance showed a shift toward higher penicillin-resistance levels, which reverted upon multiple passages on antibiotic-free media. Convergence to a homotypic resistance phenotype did not occur. Comparison of two strains of clone ST179 showed a correlation between the heteroresistant phenotype and a higher-penicillin MIC and a greater number of altered penicillin-binding proteins (PBP1a, -2b, and -2x), respectively. Therefore, heteroresistance to penicillin occurs in international multiresistant clones of\n S. pneumoniae<\/jats:italic>\n . Pneumococci may use heteroresistance to penicillin as a tool during their evolution to high penicillin resistance, because it gives the bacteria an opportunity to explore growth in the presence of antibiotics before acquisition of resistance genes.\n <\/jats:p>","DOI":"10.1073\/pnas.0702377104","type":"journal-article","created":{"date-parts":[[2007,8,17]],"date-time":"2007-08-17T20:54:19Z","timestamp":1187384059000},"page":"14098-14103","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":59,"title":["Heteroresistance to penicillin in\n Streptococcus pneumoniae<\/i>"],"prefix":"10.1073","volume":"104","author":[{"given":"Brigitte","family":"Morand","sequence":"first","affiliation":[{"name":"Institute for Infectious Diseases, University of Bern, Friedb\u00fchlstrasse 51, 3010 Bern, 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