rRNA Operon Copy Number Can Explain the Distinct Epidemiology of Hospital-Associated Methicillin-Resistant Staphylococcus aureus.
The distinct epidemiology of original hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) and early community-associated MRSA (CA-MRSA) is largely unexplained. S. aureus carries either five or six rRNA operon copies. Evidence is provided for a scenario in which MRSA has adapted to the hospital environment by rRNA operon loss (six to five copies) due to antibiotic pressure. Early CA-MRSA, in contrast, results from wild-type methicillin-susceptible S. aureus (MSSA) that acquired mecA without loss of an rRNA operon. Of the HA-MRSA isolates (n = 77), 67.5% had five rRNA operon copies, compared to 23.2% of the CA-MRSA isolates (n = 69) and 7.7% of MSSA isolates (n = 195) (P < 0.001). In addition, 105 MSSA isolates from cystic fibrosis patients were tested, because these patients are repeatedly treated with antibiotics; 32.4% of these isolates had five rRNA operon copies. For all subsets, a correlation between resistance profile and rRNA copy number was found. Furthermore, we showed that in vitro antibiotic pressure may result in rRNA operon copy loss. We also showed that without antibiotic pressure, S. aureus isolates containing six rRNA copies are more fit than isolates with five copies. We conclude that HA-MRSA and cystic fibrosis isolates most likely have adapted to an environment with high antibiotic pressure by the loss of an rRNA operon copy. This loss has facilitated resistance development, which promoted survival in these niches. However, strain fitness decreased, which explains their lack of success in the community. In contrast, CA-MRSA isolates retained six rRNA operon copies, rendering them fitter and thereby able to survive and spread in the community.
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands A.C.Fluit@umcutrecht.nl.
A C
AC
Fluit
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
M D
MD
Jansen
Centre for Infectious Disease Control Netherlands, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
T
T
Bosch
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
W T M
WT
Jansen
Centre for Infectious Disease Control Netherlands, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
L
L
Schouls
MicroArray Department & Integrative Bioinformatics Unit, Swammerdam Institute for Life Sciences, Faculty of Science (FNWI), University of Amsterdam, Amsterdam, the Netherlands.|Netherlands Bioinformatics Centre, Nijmegen, the Netherlands.
M J
MJ
Jonker
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
C H E
CH
Boel
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics; D015373:Bacterial Typing Techniques; D017714:Community-Acquired Infections / Q000453:epidemiology* / Q000382:microbiology; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D003550:Cystic Fibrosis / Q000382:microbiology; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D012329:RNA, Bacterial / Q000235:genetics*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D012407:rRNA Operon / Q000235:genetics*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D046915:Penicillin-Binding Proteins; D012329:RNA, Bacterial; C487789:mecA protein, Staphylococcus aureus
J Clin Microbiol. 2002 Nov;40(11):4289-94
12409412
Environ Microbiol. 2007 Oct;9(10):2464-74
17803772
Appl Environ Microbiol. 1983 Jul;46(1):165-70
6351743
J Hosp Infect. 2012 Jul;81(3):143-8
22622448
Lancet. 2006 Mar 4;367(9512):731-9
16517273
BMC Microbiol. 2007 Nov 06;7:99
17986343
FEMS Immunol Med Microbiol. 2004 Mar 8;40(2):101-11
15040388
Antimicrob Agents Chemother. 2008 Apr;52(4):1221-9
18212094
Appl Environ Microbiol. 1990 Jun;56(6):1875-81
16348228
J Hosp Infect. 2008 Mar;68(3):208-13
18289726
JAMA. 2001 Sep 12;286(10):1201-5
11559265
Clin Infect Dis. 2001 Oct 1;33(7):990-6
11528570
J Bacteriol. 1995 Jul;177(14):4152-6
7608093
J Infect Dis. 2004 Jul 15;190(2):311-7
15216466
Appl Environ Microbiol. 2004 Nov;70(11):6670-7
15528533
PLoS One. 2013 Jun 21;8(6):e66493
23805225
Antimicrob Agents Chemother. 2004 Jun;48(6):2295-7
15155238
Microbiology. 2006 May;152(Pt 5):1417-25
16622058
Vet Microbiol. 2009 May 12;136(3-4):277-84
19101101
FEMS Microbiol Rev. 2008 Jan;32(1):23-37
17983441
Lancet. 2010 May 1;375(9725):1557-68
20206987
Appl Environ Microbiol. 2000 Apr;66(4):1328-33
10742207
Antimicrob Agents Chemother. 2007 Apr;51(4):1497-9
17283194
Semin Respir Crit Care Med. 2005 Dec;26(6):643-9
16388433
J Antimicrob Chemother. 2001 Mar;47(3):277-83
11222560
Mo Med. 2006 Mar-Apr;103(2):129-32
16703709
Methods Mol Biol. 2007;391:1-19
18025665
J Bacteriol. 1999 Nov;181(22):6857-64
10559149
Biochimie. 1991 Jun;73(6):757-67
1764521
Int J Med Microbiol. 2013 Aug;303(6-7):324-30
23517691
J Clin Microbiol. 2000 Mar;38(3):1008-15
10698988
Methods Mol Biol. 2007;391:87-102
18025671
Curr Opin Microbiol. 2007 Oct;10 (5):428-35
17921044
PLoS One. 2007 Oct 31;2(10):e1120
17971880
Intern Med J. 2005 Dec;35 Suppl 2:S120-35
16271056