Role of Staphylococcus aureus catalase in niche competition against Streptococcus pneumoniae.
ABSTRACT Nasal colonization by Staphylococcus aureus is a major predisposing factor for subsequent infection. Recent reports of increased S. aureus colonization among children receiving pneumococcal vaccine implicate Streptococcus pneumoniae as an important competitor for the same niche. Since S. pneumoniae uses H2O2 to kill competing bacteria, we hypothesized that oxidant defense could play a significant role in promoting S. aureus colonization of the nasal mucosa. Using targeted mutagenesis, we showed that S. aureus expression of catalase contributes significantly to the survival of this pathogen in the presence of S. pneumoniae both in vitro and in a murine model of nasal cocolonization.
- SourceAvailable from: Evgeny Nudler[Show abstract] [Hide abstract]
ABSTRACT: Staphylococcus aureus (S. aureus) infections present an enormous global health concern complicated by an alarming increase in antibiotic resistance. S. aureus is among the few bacterial species that express nitric oxide synthase (bNOS), and thus can catalyze nitric oxide (NO) production from L-arginine. Here we generate an isogenic bNOS-deficient mutant in the epidemic community-acquired methicillin-resistant S. aureus (MRSA) USA300 clone to study its contribution to virulence and antibiotic susceptibility. Loss of bNOS increased MRSA susceptibility to reactive oxygen species and host cathelicidin antimicrobial peptides, which correlated with increased MRSA killing by human neutrophils and within neutrophil extracellular traps (NETs). bNOS also promoted resistance to the pharmaceutical antibiotics that act on the cell enveloppe such as vancomycin and daptomycin. Correspondingly, bNOS activity was increased upon vancomycin exposure. Surprisingly, bNOS-deficient strains gained resistance to aminoglycosides, suggesting the role of bNOS in antibiotic susceptibility is more complex than previously observed in Bacillus species. Finally, the MRSA bNOS mutant showed reduced virulence with decreased survival and smaller abscess generation in a mouse subcutaneous infection model. Together these data indicate that bNOS contributes to MRSA innate immune and antibiotic resistance phenotypes. Future development of specific bNOS inhibitors could be an attractive option to simultaneously reduce MRSA pathology and enhance its susceptibility to commonly used antibiotics.Journal of Biological Chemistry 01/2013; · 4.65 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: We describe a cutaneous abscess caused by catalase-negative methicillin-susceptible Staphylococcus aureus subsp. aureus in a patient who was concomitantly colonized with virulent USA300 methicillin-resistant S. aureus (MRSA). Sequencing of the katA gene demonstrated a thymine insertion leading to a frameshift mutation and premature truncation of catalase to 21 amino acids.Journal of clinical microbiology 10/2013; · 4.16 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Traumatology and orthopedic surgery can benefit from the use of efficient local antibiotic-eluting systems to avoid bacterial contamination of implanted materials. In this work a new percutaneous porous-wall hollow implant was successfully used as a local antibiotic-eluting device both in vitro and in vivo. The implant is a macroporous 316L stainless steel filter tube with a nominal filtration cut-off size of 200nm with one open end which was used to load the synthetic antibiotic linezolid and an opposite blind end. The antibiotic release kinetics from the device on a simulated biological fluid under in vitro conditions demonstrated an increased concentration during the first five days that subsequently was sustained for at least seven days, showing a kinetic close to a zero order release. Antibiotic-loaded implants were placed in the tibia of four sheep which were trans-surgically experimentally infected with a biofilm forming strain of Staphylococcus aureus. After 7 and 9 days post infection, sheep did not show any evidence of infection as demonstrated by clinical, pathological and microbiological findings. These results demonstrate the capability of such an antibiotic-loaded implant to prevent infection in orthopedic devices in vivo. Further research is needed to assess its possible use in traumatology and orthopedic surgery.International Journal of Pharmaceutics 05/2013; · 3.99 Impact Factor
JOURNAL OF BACTERIOLOGY, Apr. 2008, p. 2275–2278
Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Vol. 190, No. 7
Role of Staphylococcus aureus Catalase in Niche Competition against
Bonggoo Park,1Victor Nizet,2and George Y. Liu1*
Division of Pediatric Infectious Diseases and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles,
California 90048,1and Department of Pediatrics, Division of Pharmacology & Drug Discovery, School of
Medicine, University of California at San Diego, La Jolla, California 920932
Received 2 January 2008/Accepted 15 January 2008
Nasal colonization by Staphylococcus aureus is a major predisposing factor for subsequent infection. Recent
reports of increased S. aureus colonization among children receiving pneumococcal vaccine implicate Strepto-
coccus pneumoniae as an important competitor for the same niche. Since S. pneumoniae uses H2O2to kill
competing bacteria, we hypothesized that oxidant defense could play a significant role in promoting S. aureus
colonization of the nasal mucosa. Using targeted mutagenesis, we showed that S. aureus expression of catalase
contributes significantly to the survival of this pathogen in the presence of S. pneumoniae both in vitro and in
a murine model of nasal cocolonization.
Staphylococcus aureus causes a wide range of infections
ranging from minor skin infections to life-threatening invasive
diseases. The emergence of methicillin-resistant strains with
high virulence potential in both hospital and community set-
tings is contributing to a current public health crisis (9, 12, 13).
A major risk factor for S. aureus infection is antecedent colo-
nization of the nasal mucosa (19). Successful colonization de-
pends not only on the ability of S. aureus to survive host factors (4,
6) but also on coexistence with other bacteria (16, 21).
The latter concept has been underscored by two recent re-
ports that implicate Streptococcus pneumoniae as a primary
competitor for niche colonization (3, 15).
Specifically, one surveillance study performed in an area
where pneumococcal vaccination was not practiced showed
that the S. pneumoniae carriage rate in children was negatively
associated with S. aureus nasal carriage (15). The other study
showed that children with recurrent otitis media vaccinated
with the 7-valent pneumococcal vaccine had an increased in-
cidence of S. aureus-related acute otitis media and S. aureus
colonization after vaccination (3), suggesting that there is a
natural competition for colonization between S. aureus and S.
S. pneumoniae produces H2O2as an antimicrobial factor to
reduce competition by other upper respiratory pathogens, such
as Haemophilus influenzae, Neisseria meningitides, Moraxella
catarrhalis, and S. aureus (14, 16). Since S. aureus is a natural
colonizer of the human nares, we hypothesized that its success
derives in part from a relative resistance to H2O2killing by
other microflora. Here we tested this hypothesis by generating
a catalase knockout mutant strain of S. aureus and examining
the role of enzymatic H2O2inactivation in niche competition
with S. pneumoniae.
MATERIALS AND METHODS
Bacterial strains, media, and mice. S. aureus strains were cultured at 37°C in
Todd-Hewitt broth (THB) or on Todd-Hewitt agar (THA) (Difco). S. pneu-
moniae TIGR4 was cultured in THB with 0.5% yeast extract (THY) at 37°C in
a 5% CO2incubator. Eight- to 10-week old female CD1 mice were purchased
from Charles River Laboratories, Wilmington, MA. When included, antibiotics
were added at the following concentrations: 100 ?g ampicillin/ml, 50 ?g eryth-
romycin/ml, and 100 ?g spectinomycin/ml.
Generation of catalase-deficient S. aureus ?KatA mutant. In-frame allelic
replacement of the S. aureus katA gene with a spectinomycin adenyltransferase
(spec) cassette was performed using PCR-based methods as described previously
(11), with minor modifications. Primers were designed based on the previously
N315 (10). PCR was used to amplify 500 bp upstream of katA with primers katAupF
(5?-ATGGTCGACTATGACATCAACACTTGTAAC-3?) and katAupR (5?-TCA
AATATATCCTCCTCATCCCTCCACAATTTATAATAAT-3?) along with 500
bp of sequence immediately downstream of katA with primers katAdownF (5?-AA
katAdownR (5?-ATCGGATCCTACCCAGAATTACTTCGTACT-3?).The katAupR
and katAdownF primers were constructed with 25-bp 5? extensions corresponding to
the 5? and 3? ends of the spec gene, respectively. The upstream and downstream
PCR products were then combined with a 650-bp amplicon of the complete spec
gene for use as templates in a second round of PCR using primers katAupF and
katAdownR. The resultant PCR amplicon, containing an in-frame substitution of
katA with spec, was subcloned into temperature-sensitive vector pMAD (1) to
create the knockout plasmid. This vector was transformed initially into permis-
sive S. aureus strain RN4220 and then into S. aureus strain Newman by electro-
poration. Transformants were grown at 30°C and shifted to the nonpermissive
temperature for plasmid replication (40°C), and differential antibiotic selection
and blue-white color selection with 5-bromo-4-chloro-3-indolyl-?-D-galacto-
pyranoside (X-Gal) were used to identify candidate mutants. Allelic replacement
of the katA allele was confirmed unambiguously by PCRs that documented
targeted insertion of spec and the absence of katA in chromosomal DNA isolated
from the final mutant, which was designated the ?KatA mutant.
Complementation studies. Primers katAF_KpnI (5?-ATAGGTACCTCCCAT
GGTAAAGCCAAGAG-3?) and katAR_BamHI (5?-ATAGGATCCTTTACGC
GCACGTTAAACAC-3?) were used to amplify the katA gene from the chro-
mosome of wild-type (WT) S. aureus strain Newman. The fragment was
directionally cloned into the shuttle expression vector pDCerm (8), and the
recombinant plasmid (pKatA) was used to transform the S. aureus ?KatA mu-
tant by electroporation. For the complementation studies, the isogenic WT and
?KatA S. aureus strains were transformed with the control pDCerm plasmid.
Strains containing the pDCerm or pKatA plasmid were maintained in THB or on
THA containing erythromycin.
H2O2susceptibility assay. H2O2susceptibility assays were performed using
overnight S. aureus cultures grown at 37°C with shaking. Bacteria were harvested
by centrifugation, suspended in phosphate-buffered saline (PBS) at a concentra-
* Corresponding author. Mailing address: Department of Pediatrics,
Cedars-Sinai Medical Center, 8700 Beverly Blvd., Room 4221, Los
Angeles, CA 90048. Phone: (310) 423-4471. Fax: (310) 423-8284. E-
?Published ahead of print on 25 January 2008.
tion of 5 ? 107CFU/ml, and mixed with various concentrations of H2O2. The
killing assay was terminated after 2 h of incubation at 37°C by addition of 5,000
U/ml of catalase (Sigma), which was followed by enumeration of surviving bac-
terial CFU on THA.
Susceptibility of S. aureus to S. pneumoniae killing in vitro. (i) Plate assay.
Overnight S. aureus cultures were centrifuged, washed, and suspended in PBS at
a concentration of 5 ? 108CFU/ml. Two hundred microliters was plated on THY
plates, and a paper disk impregnated with 1.5 ? 109log-phase S. pneumoniae
cells was placed in the center of each plate. The zone of S. aureus growth
inhibition was measured after 24 h of incubation at 37°C in the presence of 5%
(ii) Liquid culture-based assay. Overnight S. aureus cultures were centrifuged,
washed in PBS, diluted to obtain a concentration of 1 ? 109CFU/ml, and mixed
with log-phase S. pneumoniae at a ratio of 1:1, 1:5, or 1:10 in THY. After 4 h of
incubation at 37°C in the presence of 5% CO2, the remaining H2O2was
quenched with 50 ?l of a 5,000-U/ml exogenous catalase solution, and the
surviving S. aureus cells were diluted in PBS and plated on THA plates. As a
control, parallel experiments were performed in an identical fashion in the
presence of 1,000 U/ml catalase.
Murine nasal cocolonization studies. Mice were inoculated intranasally with a
10 ?l of a mixture containing 108WT cells and 108S. aureus ?KatA cells. After
30 min, the mice were divided into two groups and given either 10 ?l of THY or
3 ? 108early-stationary-phase S. pneumoniae cells in THY. After 3 days, the
mice were sacrificed, the nasal tissue was homogenized and vortexed for 5 min in
PBS, and the CFU were enumerated on THA with or without spectinomycin
after appropriate dilution. Occasional contaminants were excluded during count-
ing of the CFU by the morphology or color of the bacterial colonies. Animal
experimentation guidelines were followed in the animal studies.
Statistical analysis. The significance of experimental differences in H2O2
sensitivity and S. pneumoniae killing in vitro was evaluated by using the unpaired
Student t test. The results of the mouse in vivo challenge studies were evaluated
by using the nonparametric two-tailed Wilcoxon and Mann-Whitney tests.
To address the role of catalase in niche competition, a KatA
deletion mutant of S. aureus strain Newman was generated by
allelic replacement of the katA gene with a spectinomycin
acetyltransferase cassette. Deletion of the katA gene was con-
firmed by PCR and by the absence of effervescence upon
exposure of the ?KatA mutant to H2O2(data not shown).
To assess the effect of katA deletion on S. aureus suscepti-
bility to H2O2, the WT and ?KatA strains were exposed to a
range of H2O2concentrations in PBS. In the absence of cata-
lase, S. aureus was highly susceptible to H2O2killing (Fig. 1A).
Complementation with pKatA restored the ability of the
?KatA mutant to resist H2O2killing (Fig. 1B). The pDCerm
vector used for complementation was also placed into the
?KatA mutant, and it had no impact on H2O2susceptibility.
Since S. pneumoniae produces H2O2in quantities sufficient
to kill other bacterial species (14), we tested whether catalase
has an important survival function for S. aureus when it is
cultured in the presence of S. pneumoniae. As shown in Fig.
2A, a disk impregnated with log-phase S. pneumoniae cells
partially inhibited growth of the WT S. aureus strain on a THY
plate but had a much more profound effect on the growth of
the isogenic ?KatA mutant.
In a more quantitative liquid culture-based assay, at a ratio
of S. aureus to S. pneumoniae of 1:1, minimal killing of WT or
mutant S. aureus was noted (Fig. 2B). However, at a ratio of 1:5
or 1:10, the survival of the ?KatA mutant in the presence of S.
pneumoniae was reduced by as much as 8 logs compared to the
survival of the parent strain (Fig. 2B). The differential killing
was most likely a result of H2O2production by S. pneumoniae,
since no killing of S. aureus was observed if an exogenous
source of catalase was added to the culture at the start of the
assay (Fig. 2B). Complementation with pKatA restored the
ability of the ?KatA mutant to resist S. pneumoniae killing
Next, to extend the biological relevance of these findings, the
role of S. aureus catalase was assessed using a murine model of
nasal colonization. In this study, mice were inoculated intra-
nasally with equal numbers of WT and ?KatA S. aureus cells
with or without S. pneumoniae. After 3 days, the surviving WT
FIG. 1. S. aureus catalase confers resistance to H2O2 killing.
(A) Susceptibility of WT and ?KatA S. aureus strains to different
concentrations of H2O2. (B) Restoration of resistance to H2O2killing
upon complementation of the ?KatA mutant with pKatA. All exper-
iments were performed at least three times, and similar results were
FIG. 2. Catalase protects S. aureus against S. pneumoniae killing in
vitro. (A) Effect of a disk impregnated with S. pneumoniae on growth
of the WT or ?KatA S. aureus strain. (B) Survival of the WT or ?KatA
S. aureus strain upon coculture with S. pneumoniae at ratios of 1:1, 1:5,
and 1:10. (C) Restoration of resistance to S. pneumoniae killing upon
complementation of the ?KatA mutant with pKatA. All experiments
were repeated at least three times, and similar results were obtained.
2276PARK ET AL. J. BACTERIOL.
and ?KatA cells were harvested from the noses of the mice. As
shown in Fig. 3, the survival of the WT strain and the survival
of the ?KatA strain in noses of mice did not differ significantly
at day 3 when they were inoculated alone, but a notable dif-
ference in the levels of survival in favor of WT S. aureus was
apparent in mice given S. pneumoniae as a competitor for the
Multiple studies have shown that colonization of the upper
airway with S. pneumoniae is negatively correlated with S.
aureus colonization, and introduction of the S. pneumoniae
vaccine has increased the rate of S. aureus nasal colonization
(3, 15). By eradicating carriage of S. pneumoniae vaccine
strains, immunization removes an important niche competitor
that utilizes H2O2to restrict colonization by other bacteria. In
this study, we showed that the S. aureus catalase is a major
factor in S. aureus defense against S. pneumoniae killing due to
neutralization of secreted H2O2. H2O2is used as an antimi-
crobial factor by many other microbes (2, 18), including Strep-
tococcus sanguinis in the oral cavity and lactobacilli in the
vagina, two sites frequently cocolonized by S. aureus. Thus, it
could be speculated that in S. aureus catalase is an important
tool for securing a niche on multiple mucosal surfaces in the
human host. The presence of catalase may also explain the
preferential survival of WT S. aureus compared to the ?KatA
mutant in the cotton rat model of nasal colonization previously
reported by Cosgrove and coworkers (5).
S. aureus encodes a number antioxidants, including, alkyl
hydroperoxide reductase, and staphyloxanthin, which may sup-
plement catalase in defense against H2O2-producing organ-
isms, such as S. pneumoniae.
Although catalase is a factor produced by many bacteria,
several studies have failed to establish a function for catalase in
systemic virulence (7, 17, 20). Our finding that catalase plays an
important role in S. aureus in mucosal niche competition points
to an alternative role that catalase could play in the most
proximal steps of disease pathogenesis. The S. aureus catalase
could thus be a novel pharmacologic target for decolonization
strategies, a desirable therapeutic endpoint in many clinical
We thank Terence Doherty for critical reading of the manuscript.
This work was supported by a Burroughs-Wellcome Career Award
and by National Institutes of Health grant AI074832 to G. Y. Liu.
1. Arnaud, M., A. Chastanet, and M. Debarbouille. 2004. New vector for
efficient allelic replacement in naturally nontransformable, low-GC-content,
gram-positive bacteria. Appl. Environ Microbiol. 70:6887–6891.
2. Atassi, F., D. Brassart, P. Grob, F. Graf, and A. L. Servin. 2006. Lactoba-
cillus strains isolated from the vaginal microbiota of healthy women inhibit
Prevotella bivia and Gardnerella vaginalis in coculture and cell culture.
FEMS Immunol. Med. Microbiol. 48:424–432.
3. Bogaert, D., A. van Belkum, M. Sluijter, A. Luijendijk, R. de Groot, H. C.
Rumke, H. A. Verbrugh, and P. W. Hermans. 2004. Colonisation by Strep-
tococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet
4. Cole, A. M., S. Tahk, A. Oren, D. Yoshioka, Y. H. Kim, A. Park, and T. Ganz.
2001. Determinants of Staphylococcus aureus nasal carriage. Clin. Diagn.
Lab Immunol. 8:1064–1069.
5. Cosgrove, K., G. Coutts, I. M. Jonsson, A. Tarkowski, J. F. Kokai-Kun, J. J.
Mond, and S. J. Foster. 2007. Catalase (KatA) and alkyl hydroperoxide
reductase (AhpC) have compensatory roles in peroxide stress resistance and
are required for survival, persistence, and nasal colonization in Staphylococ-
cus aureus. J. Bacteriol. 189:1025–1035.
6. Gonzalez-Zorn, B., J. P. Senna, L. Fiette, S. Shorte, A. Testard, M. Chignard, P.
Courvalin, and C. Grillot-Courvalin. 2005. Bacterial and host factors implicated
in nasal carriage of methicillin-resistant Staphylococcus aureus in mice. Infect.
7. Horsburgh, M. J., M. O. Clements, H. Crossley, E. Ingham, and S. J. Foster.
2001. PerR controls oxidative stress resistance and iron storage proteins and
is required for virulence in Staphylococcus aureus. Infect. Immun. 69:3744–
8. Jeng, A., V. Sakota, Z. Li, V. Datta, B. Beall, and V. Nizet. 2003. Molecular
genetic analysis of a group A Streptococcus operon encoding serum opacity
factor and a novel fibronectin-binding protein, SfbX. J. Bacteriol. 185:1208–
9. Klevens, R. M., M. A. Morrison, J. Nadle, S. Petit, K. Gershman, S. Ray,
L. H. Harrison, R. Lynfield, G. Dumyati, J. M. Townes, A. S. Craig, E. R.
Zell, G. E. Fosheim, L. K. McDougal, R. B. Carey, and S. K. Fridkin. 2007.
Invasive methicillin-resistant Staphylococcus aureus infections in the United
States. JAMA 298:1763–1771.
10. Kuroda, M., T. Ohta, I. Uchiyama, T. Baba, H. Yuzawa, I. Kobayashi, L. Cui,
A. Oguchi, K. Aoki, Y. Nagai, J. Lian, T. Ito, M. Kanamori, H. Matsumaru,
A. Maruyama, H. Murakami, A. Hosoyama, Y. Mizutani-Ui, N. K. Taka-
hashi, T. Sawano, R. Inoue, C. Kaito, K. Sekimizu, H. Hirakawa, S. Kuhara,
S. Goto, J. Yabuzaki, M. Kanehisa, A. Yamashita, K. Oshima, K. Furuya, C.
Yoshino, T. Shiba, M. Hattori, N. Ogasawara, H. Hayashi, and K. Hira-
matsu. 2001. Whole genome sequencing of methicillin-resistant Staphylo-
coccus aureus. Lancet 357:1225–1240.
11. Liu, G. Y., A. Essex, J. T. Buchanan, V. Datta, H. M. Hoffman, J. F. Bastian,
J. Fierer, and V. Nizet. 2005. Staphylococcus aureus golden pigment impairs
neutrophil killing and promotes virulence through its antioxidant activity. J.
Exp. Med. 202:209–215.
12. Miller, L. G., F. Perdreau-Remington, G. Rieg, S. Mehdi, J. Perlroth, A. S.
Bayer, A. W. Tang, T. O. Phung, and B. Spellberg. 2005. Necrotizing fasciitis
caused by community-associated methicillin-resistant Staphylococcus aureus
in Los Angeles. N. Engl. J. Med. 352:1445–1453.
FIG. 3. Catalase protects S. aureus against S. pneumoniae killing in
a murine model of nasal colonization. Mice were inoculated intrana-
sally with a 1:1 mixture of the WT and ?KatA S. aureus strains. After
30 min, the mice were inoculated in the same nostrils with either buffer
or S. pneumoniae at a ratio of S. pneumoniae to S. aureus of 3:1.
Surviving bacteria from the nostrils were quantitated after 3 days. The
graph on the left shows the ratios of the surviving WT S. aureus strain
to the surviving the ?KatA S. aureus mutant for individual mice. The
numbers of surviving WT and ?KatA S. aureus CFU recovered from
each mouse are plotted on the right. Mice that were poorly colonized
(?5 WT CFU and ?5 ?KatA CFU as enumerated on THA plates)
were excluded from the surviving ratio plot (left) but were included in
the survival graphs on the right. The data were compiled from three
experiments performed in the same way. The minimum detection level
of the assay is 20 CFU. S.p, S. pneumoniae.
VOL. 190, 2008S. AUREUS CATALASE AND NICHE COMPETITION2277
13. Moran, G. J., A. Krishnadasan, R. J. Gorwitz, G. E. Fosheim, L. K. McDougal,
R. B. Carey, and D. A. Talan. 2006. Methicillin-resistant S. aureus infections
among patients in the emergency department. N. Engl. J. Med. 355:666–674.
14. Pericone, C. D., S. Park, J. A. Imlay, and J. N. Weiser. 2003. Factors
contributing to hydrogen peroxide resistance in Streptococcus pneumoniae
include pyruvate oxidase (SpxB) and avoidance of the toxic effects of the
Fenton reaction. J. Bacteriol. 185:6815–6825.
15. Regev-Yochay, G., R. Dagan, M. Raz, Y. Carmeli, B. Shainberg, E. Derazne,
G. Rahav, and E. Rubinstein. 2004. Association between carriage of Strep-
tococcus pneumoniae and Staphylococcus aureus in children. JAMA 292:
16. Regev-Yochay, G., K. Trzcinski, C. M. Thompson, R. Malley, and M. Lip-
sitch. 2006. Interference between Streptococcus pneumoniae and Staphylo-
coccus aureus: in vitro hydrogen peroxide-mediated killing by Streptococcus
pneumoniae. J. Bacteriol. 188:4996–5001.
17. Soler-Garcia, A. A., and A. E. Jerse. 2007. Neisseria gonorrhoeae catalase is
not required for experimental genital tract infection despite the induction of
a localized neutrophil response. Infect. Immun. 75:2225–2233.
18. Uehara, Y., K. Kikuchi, T. Nakamura, H. Nakama, K. Agematsu, Y.
Kawakami, N. Maruchi, and K. Totsuka. 2001. H2O2produced by viridans
group streptococci may contribute to inhibition of methicillin-resistant
Staphylococcus aureus colonization of oral cavities in newborns. Clin. Infect.
19. van Belkum, A. 2006. Staphylococcal colonization and infection: homeostasis
versus disbalance of human (innate) immunity and bacterial virulence. Curr.
Opin. Infect. Dis. 19:339–344.
20. Vergauwen, B., M. Herbert, and J. J. Van Beeumen. 2006. Hydrogen perox-
ide scavenging is not a virulence determinant in the pathogenesis of Hae-
mophilus influenzae type b strain Eagan. BMC Microbiol. 6:3.
21. Zarate, G., and M. E. Nader-Macias. 2006. Influence of probiotic vaginal
lactobacilli on in vitro adhesion of urogenital pathogens to vaginal epithelial
cells. Lett. Appl. Microbiol. 43:174–180.
2278PARK ET AL.J. BACTERIOL.