title: Heteroresistance to penicillin in Streptococcus pneumoniae.
abstract: Heteroresistance to beta-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 Streptococcus pneumoniae. 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(23F)-1, Spain(9V)-3, Spain(14)-5, Hungary(19A)-6, South Africa(19A)-13, Taiwan(23F)-15, and Finland(6B)-12). Heteroresistant strains had penicillin minimal inhibitory concentrations (MICs) (for the majority of cells) in the intermediate- to high-level range (0.19-2.0 mug/ml). PAP curves suggested the presence of subpopulations also for the highly penicillin-resistant strains Taiwan(19F)-14, Poland(23F)-16, CSR(19A)-11, and CSR(14)-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 S. pneumoniae. 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.
authors: Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, 3010 Bern, Switzerland.
authors: Brigitte
authors: B
authors: Morand
authors: Kathrin
authors: K
authors: Mühlemann
mesh_terms: D024881:Drug Resistance, Bacterial; D005843:Geography; D006461:Hemolysis; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010406:Penicillins / Q000494:pharmacology*; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D010406:Penicillins
references: J Clin Microbiol. 2006 Jun;44(6):2032-8
references: 16757594
references: Antimicrob Agents Chemother. 2006 Sep;50(9):2946-50
references: 16940086
references: J Clin Microbiol. 2001 Sep;39(9):3379-81
references: 11526184
references: J Bacteriol. 2004 Jun;186(12):3721-9
references: 15175285
references: J Exp Med. 1944 Feb 1;79(2):137-58
references: 19871359
references: Antimicrob Agents Chemother. 2006 Dec;50(12):4062-9
references: 17000738
references: J Bacteriol. 1989 Feb;171(2):874-9
references: 2536684
references: Antimicrob Agents Chemother. 1986 Jan;29(1):85-92
references: 3488015
references: J Med Microbiol. 2003 Aug;52(Pt 8):605-7
references: 12867551
references: Antimicrob Agents Chemother. 2002 Jan;46(1):24-30
references: 11751106
references: Antimicrob Agents Chemother. 2006 Dec;50(12):4053-61
references: 17000741
references: Antimicrob Agents Chemother. 1994 Nov;38(11):2590-8
references: 7872753
references: Microbiology. 1998 Nov;144 ( Pt 11):3049-60
references: 9846740
references: Antimicrob Agents Chemother. 2004 Sep;48(9):3563-6
references: 15328127
references: J Infect Dis. 2006 May 1;193(9):1296-303
references: 16586368
references: Mol Microbiol. 1999 Aug;33(4):673-8
references: 10447877
references: J Antimicrob Chemother. 2001 Apr;47(4):399-403
references: 11266410
references: Mol Microbiol. 1994 May;12(3):505-15
references: 8065267
references: Eur J Clin Microbiol Infect Dis. 1993;12 Suppl 1:S13-8
references: 8477757
references: Mol Microbiol. 1993 Aug;9(3):635-43
references: 8412708
references: Antimicrob Agents Chemother. 1991 Jan;35(1):124-9
references: 2014967
references: J Clin Microbiol. 2003 Jan;41(1):267-72
references: 12517859
references: Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1550-5
references: 11830670
references: J Infect Dis. 2003 Feb 15;187(4):589-96
references: 12599075
references: J Clin Microbiol. 2001 Jul;39(7):2565-71
references: 11427569
references: Proc Natl Acad Sci U S A. 1989 Nov;86(22):8842-6
references: 2813426
references: Int J Tuberc Lung Dis. 2001 Apr;5(4):339-45
references: 11334252
references: J Infect Dis. 2000 Oct;182(4):1153-60
references: 10979912
references: Antimicrob Agents Chemother. 1994 Apr;38(4):724-8
references: 8031036
references: J Antimicrob Chemother. 2002 Dec;50 Suppl S2:1-5
references: 12556427
references: J Clin Microbiol. 2005 Sep;43(9):4696-703
references: 16145129