Staphylococcal colonization and infection: Homeostasis versus disbalance of human (innate) immunity and bacterial virulence

Current Opinion in Infectious Diseases

Volumn 19, Issue 4, 2006, Pages 339-344

  Van Belkum, Alex ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Infection; Methicillin resistant Staphylococcus aureus; Nasal carriage; Staphylococcus aureus

Indexed keywords

BACTERIAL PROTEIN; ENTEROTOXIN; LEUKOCIDIN; PANTON VALENTINE LEUKOCIDIN; RECOMBINANT PROTEIN; TOLL LIKE RECEPTOR 2; UNCLASSIFIED DRUG; VIRULENCE FACTOR;

ANTIBIOTIC RESISTANCE; ANTIBODY RESPONSE; BACTERIAL INFECTION; BACTERIAL VIRULENCE; EARLY DIAGNOSIS; ENZYME LINKED IMMUNOSORBENT ASSAY; HOST PATHOGEN INTERACTION; HUMAN; INFECTION CONTROL; INNATE IMMUNITY; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; NONHUMAN; REVIEW; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS INFECTION; TOXIC SHOCK SYNDROME; VENTILATOR ASSOCIATED PNEUMONIA;

ANTIBODIES, BACTERIAL; HOMEOSTASIS; HUMANS; IMMUNITY, NATURAL; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; VIRULENCE;

EID: 33745604928     PISSN: 09517375     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.qco.0000235159.40184.61     Document Type: Review

References (46)

1. Wertheim HFL, Melles DC, Vos MC, et al. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis 2005; 5:751-762. Timely review on staphylococcal carriage in the human nose. Human and demographic determinants of carriage are tabulated as are bacterial factors important in establishing healthy populations of resident bacteria. Simple Mendelian traits will probably never be able to explain the host-bacterium interaction since exposure frequency and other multifactorial phenomena have been shown to be important denominators. There is an important need to identify those (colonized) patients that are at an increased risk for developing staphylococcal infections. In particular, the immunological basis of successful colonization (or noncolonization) requires our undivided attention.
2. Wertheim HF, Vos MC, Ott A, et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus noncarriers. Lancet 2004; 364:703-705.
3. Tiemersma EW, Monnet DL, Bruinsma N, et al. Staphylococcus aureus bacteremia. Europe Emerg Infect Dis 2006; 11:1798-1799.
4. Gould IM. The clinical significance of methicillin-resistant Staphylococcus aureus. J Hosp Infect 2005; 61:277-282.
5. Nouwen JL, Ott A, Vandenbergh MFQ, et al. Predicting the Staphylococcus aureus nasal carriage state: derivation and validation of a culture rule. Clin Infect Dis 2004; 39:806-811.
6. Nouwen JL, Fieren MWJA, Snijders S, et al. Persistent (not intermittent) nasal carriage of Staphylococcus aureus is the determinant of chronic peritoneal dialysis-related infections. Kidney Int 2005; 67:1084-1092. First study showing that the type of carriage pattern (in addition to being a carrier per se) is clinically important: the high load persistent S. aureus nasal carriers are at a clearly increased risk for acquiring staphylococcal infections compared with low-level intermittent carriers.
7. Boyce JM, Havill NL, Maria B. Frequency and possible infection control implications of gastrointestinal colonization with methicillin-resistant Staphylococcus aureus. J Clin Microbiol 2005; 43:5992-5995. The authors substantiate that gastrointestinal carriage of MRSA is frequent, often not diagnosed and may lead to further dissemination of MRSA in clinical settings. Gut carriage, though probably not as important as nasal carriage of S. aureus should not be overlooked when tracking MRSA in clinical settings.
8. Guillemot D, Bonacorsi S, Blanchard JS, et al. Amoxicillin-clavulanate therapy increases childhood nasal colonization by methicillin-susceptible Staphylococcus aureus strains producing high levels of penicillinase. Antimicrob Agents Chemother 2004; 48:4618-4623.
9. Dall'Antonia M, Coen PG, Wilks M, et al. Competition between methicillin-sensitive and resistant Staphylococcus aureus in the anterior nares. J Hosp Infect 2005; 61:62-67. Very simple but elegant study that finally confirms what many were already expecting to be the case: MRSA and MSSA compete for the same anatomical niche. This revitalizes the concept of using bacterial interference in the out-competition of deleterious bugs.
10. Becker K, Pagnier I, Schuhen B, et al. Does nasal cocolonization by methicillin-resistant coagulase negative staphylococci and MSSA strains occur frequently enough to represent a risk of false positive MRSA determinations by molecular methods? J Clin Microbiol 2005; 44:229-231.
11. Huletsky A, Lebel P, Picard FJ, et al. Identification of methicillin-resistant Staphylococcus aureus carriage in less than 1 hour during a hospital surveillance program. Clin Infect Dis 2005; 40:976-981. This was the first report on the successful clinical application of a quantitative, real-time polymerase chain reaction (PCR) test for the detection of MRSA. Data show that in a high-incidence setting the SCCmec-specific PCR assay may be useful in infection control policies. Whether the test is as valuable in low-endemic settings needs to be verified by additional clinical trials.
12. Warren DK, Liao RS, Merz LR, et al. Detection of methicillin-resistant Staphylococcus aureus directly from nasal swab specimens by a real-time PCR assay. J Clin Microbiol 2004; 42:5578-5581.
13. Mellmann A, Friedrich AW, Rosenkotter N, et al. Automated DNA sequence based early warning system for the detection of methicillin-resistant Staphylococcus aureus outbreaks. PLOS Med 2006; 3:1-8. Identifies an experimental approach to developing an early warning system flagging MRSA type identity. Rapid sequence-based analysis of the protein A gene generates data that can be subjected to computerized analysis. Matches in sequence motifs are reported signifying the second (third, fourth ...) occurrence of a given microbial isolate. Should have infection control value.
14. Tenover FC, McDougal LK, Goering RV, et al. Characterisation of a strain of community-acquired methicillin-resistant Staphylococcus aureus widely disseminated in the United States. J Clin Microbiol 2006; 44:108-118.
15. Sola C, Cortes P, Saka HA, et al. Evolution and molecular characterisation of methicillin-resistant Staphylococcus aureus epidemic and sporadic clones in Cordoba, Argentina. J Clin Microbiol 2006; 44:192-200.
16. Adesida S, Boelens H, Babajide B, et al. Major epidemic clones of Staphylococcus aureus in Nigeria. Microb Drug Resist 2005; 11:115-121.
17. François P, Huyghe A, Charbonnier Y, et al. Use of an automated multiple locus variable number of tandem repeat-based method for rapid and high-throughput genotyping of Staphylococcus aureus isolates. J Clin Microbiol 2005; 43:3346-3355.
18. Lindsay JA, Moore CE, Day NP, et al. Micro-arrays reveal that each of the ten dominant lineages of Staphylococcus aureus has a unique combination of surface associated and regulatory genes. J Bacteriol 2006; 188:669-676. Using micro-arrays these authors distinguish the staphylococcal core genome elements from core-variable elements. The latter are thought to have a common ancestor but prolonged periods of independent evolution. In addition, various mobile elements capable of horizontal transfer are identified. Again, disease-invoking capacity is present among many strains in all of the 10 different lineages identified.
19. Robinson DA, Monk AB, Cooper JE, et al. Evolutionary genetics of the accessory gene regulator (agr) locus in Staphylococcus aureus. J Bacteriol 2005; 187:8312-8321.
20. Prunier AL, Leclercq R. Role of mutS and mutL genes in hypermutability and recombination in Staphylococcus aureus. J Bacteriol 2005; 187:3455-3464. It is demonstrated that in S. aureus variation in the methyl mismatch repair system guided by MutS and MutL defines the mutator state of a strain. Hypermutability does not affect homologous recombination but the mutator phenotype could be clearly linked to mutS and mutL mutations. This has obvious consequences for the biology of an organism that will be frequently subjected to strong selective biological pressures.
21. Hughes AL, Friedman R. Nucleotide substitution and recombination at orthologous loci in Staphylococcus aureus. J Bacteriol 2005; 187:2698-2704.
22. Pan ES, Diep BA, Charlebois ED, et al. Population dynamics of nasal strains of methicillin-resistant Staphylococcus aureus and their relation to community associated disease activity. J Infect Dis 2005; 192:811-818.
23. Wertheim HFL, Van Leeuwen WB, Snijders S, et al. Associations between Staphylococcus aureus genotype, infection and in-hospital mortality: a nested case control study. J Infect Dis 2005; 192:1196-1200. The data presented show that certain clonal clusters of S. aureus are more or less invasive when compared with others. Also, successful clones, as evidenced by their occurrence in clonal clusters, tend to generate more mortality than incidental types, presenting as singletons.
24. Van Leeuwen WB, Melles DC, Alaidan A, et al. Host- and tissue-specific traits of Staphylococcus aureus. J Bacteriol 2005; 187:4584-4591.
25. Boyce JM, Havill NL. Nosocomial antibiotic associated diarrhea associated with enterotoxin producing strains of methicillin-resistant Staphylococcus aureus. Am J Gastroenterol 2005; 100:1828-1834.
26. Kropec A, Maria-Litran T, Jefferson KK, et al. Poly-N-acetylglucosamine production in Staphylococcus aureus is essential for virulence in murine models of systemic infection. Infect Immun 2005; 73:6868-6876.
27. Weidenmaier C, Peschel A, Xiong YQ, et al. Lack of wall teichoic acids in Staphylococcus aureus leads to reduced interactions with endothelial cells and attenuated virulence in a rabbit model of endocarditis. J Infect Dis 2005; 191:1771-1777.
28. Visser L, De Heer HJ, Boven LA, et al. Pro-inflammatory bacterial peptidoglycan as a co-factor for the development of central nervous system autoimmune disease. J Immunol 2005; 174:808-816. Peptidoglycan may provide a physiological trigger of dendritic cell maturation and may disrupt normal tolerance towards self-antigens. Staphylococcal peptidoglycan can induce experimental autoimmune encephalomyelitis, a model system for the study of multiple sclerosis in humans. The association between staphylococcal infection, carriage and development of multiple sclerosis in humans is certainly worth investigating.
29. Dziarski R, Gupta D. Staphylococcus aureus peptidoglycan is a toll-like receptor 2 activator: a re-evaluation. Infect Immun 2005; 73:5212-5216.
30. Hadley JS, Wang JE, Foster SJ, et al. Peptidoglycan of Staphylococcus aureus up-regulates monocyte expression of CD14, toll-like receptor 2 (TLR2) and TLR4 in human blood: possible implications for priming of lipopolysaccharide signalling. Infect Immun 2005; 73:7613-7619.
31. Genestier AL, Michallet MC, Prevost G, et al. Staphylococcus aureus Panton-Valentine leukocidin directly targets mitochondria and induces Bax independent apoptosis of human neutrophils. J Clin Invest 2005; 115:3117-3127. Excellent paper describing the molecular features of PVL toxicity. A very elegant multidisciplinary approach is used to show that PVL essentially generates pores in the mitochondrial membrane, a process that subsequently triggers cellular apoptosis. State-of-the-art enzymology and biochemistry in combination with microscopy and patho-physiology. Recommended reading for all.
32. Holtfreter S, Broker BM. Staphylococcal superantigens: do they play a role in sepsis? Arch Immunol Ther Exp 2005; 53:13-27. Timely review on the activity of and immune responses against staphylococcal superantigens.
33. Ferry T, Thomas D, Genestier AL, et al. Comparative prevalence of super-antigen genes in Staphylococcus aureus isolates causing sepsis with and without septic shock. Clin Infect Dis 2005; 41:771-777.
34. Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. New Engl J Med 2005; 352:1445-1453. Although necrotizing fasciitis was not frequently associated with S. aureus infection, an alarming rise in the number of community-based cases caused by this pathogen was recently observed. In particular, ST8, mec-type 4, PVL-positive isolates were cultured from the lesions, suggesting that the increased incidence of this serious staphylococcal disease was due to clonal dissemination of a single, highly virulent S. aureus strain.
35. Zahar JR, Clec'h C, Tafflet M, et al. Is methicillin-resistance associated with a worse prognosis in Staphylococcus aureus ventilator-associated pneumonia? Clin Infect Dis 2005; 41:1224-1231.
36. Gastmeier P, Sohr D, Geffers C, et al. Mortality risk factors with nosocomial Staphylococcus aureus infections in intensive care units: results from the German Nosocomial Infection Surveillance System (KISS). Infection 2005; 33:50-55. The most extensive search for differences in virulence between MRSA and MSSA ever performed. This German study involved 505 487 intensive care patients, 6888 cases of nosocomial pneumonia, 2357 cases of blood stream infection, and 5years of data gathering from 274 ICUs. The authors concluded that though nosocomial pneumonia and primary MRSA blood stream infection may be associated with death, a clear cause-effect relationship of severity of illness and MRSA remains to be determined. Even this gigantic database, however, is apparently inconclusive. This suggests that if differences in invasiveness between MRSA and MSSA do exist, these will be minor.
37. Melles DC, Gorkink RF, Boelens HA, et al. Natural population dynamics and expansion of pathogenic clones of Staphylococcus aureus. J Clin Invest 2004; 114:1732-1740.
38. Kuroda M, Yamashita A, Hirakawa H, et al. Whole genome sequence of Staphylococcus saprophyticus reveals the pathogenesis of uncomplicated urinary tract infection. Proc Natl Acad Sci U S A 2005; 102:13272-13277. Yet another full paper based on a single genome sequence. In this case the authors illustrated that cross-species comparisons are very useful in assessing differential virulence potential between species causing similar disease phenotypes. This approach is worth extrapolating to a detailed assessment using all available pathogen genome sequences. This approach allows for the tentative identification of putatively important virulence factors.
39. Rooijakkers SHM, Van Kessel KPM, Van Strijp JAG. Staphylococcal innate immune evasion. Trends Microbiol 2005; 13:596-601. Excellent review paper.
40. Foster TJ. Immune evasion by staphylococci. Nature Rev Microbiol 2005; 3:948-958. Another excellent review paper.
41. Rooijakkers SHM, Ruyken M, Roos A, et al. Immune evasion by staphylococcal complement inhibitor that acts on C3 convertases. Nature Immunol 2005; 6:920-927. One of the most exciting papers published in the staphylococcal research field last year. It describes the characterization of a novel molecule with complement-inhibiting capacities. This molecule displays obvious anti-inflammatory activity, something that may be translated into therapeutic intervention. The authors showed that S. aureus is capable of modulating or maybe even circumventing human innate immune reactivity, a feature that may be basic to the apparent ecological success of the staphylococci. Why the inhibitor is part of a bacteriophage is subject to further research.
42. Voyich VM, Braughton KR, Sturdevant DE, et al. Insights into mechanisms used by Staphylococcus aureus to avoid destruction by human neutrophils. J Immunol 2005; 175:3907-3919. This was yet another paper addressing innate immune evasion by S. aureus, a popular recent subtheme. The molecular data presented suggest that S. aureus actively combats neutrophil-mediated killing by switching on different sets of genes when being internalized. Capsule synthesis, oxidative stress genes and several virulence genes were upregulated upon phagocytosis. Apparently, S. aureus uses different gene expression profiles depending on local conditions. This facilitates a novel mode of innate immune escape.
43. Fournier B, Philpott DJ. Recognition of Staphylococcus aureus by the innate immune system. Clin Microbiol Rev 2005; 18:521-540. Yet another excellent review paper.
44. Dryla A, Prustomersky S, Gelbman D, et al. Comparison of antibody repertoires against Staphylococcus aureus in healthy individuals and in acutely infected patients. Clin Diagn Lab Immunol 2005; 12:387-398. This paper provided the first description of the antistaphylococcal humoral immune responses in healthy carriers and infected patients. The use of recombinant antigens does not generate a complete and comprehensive analysis of all (clinically) relevant antibody responses but it does illustrate the experimental possibilities and generates many hypotheses for future investigations.
45. Moore CE, Segal S, Berendt AR, et al. Lack of association between toll-like receptor 2 polymorphisms and susceptibility to severe disease caused by Staphylococcus aureus. Clin Diagn Lab Immunol 2004; 11:1194-1197.
46. Gonzalez-Zorn B, Senna JPM, Fiette L, et al. Bacterial and host factors implicated in nasal carriage of methicillin-resistant Staphylococcus aureus in mice. Infect Immun 2005; 73:1847-1851.