Staphylococcus aureus in patients with cystic fibrosis: An epidemiological analysis using a combination of traditional and molecular methods

Goering, Richard V.; Bauernfeind, A.; Lenz, W; Przyklenk, B.

doi:10.1007/bf01644187

Cited by 22 publications

(14 citation statements)

References 11 publications

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“…This propensity to cause chronic infections is thought to be related, at least in part, to the persistence of SCVs within nonphagocytic host cells (39). Antibiotic treatments often are ineffective against S. aureus infecting CF lungs, and relapsing infections are often observed (13,18). These relapsing infections are thought to be caused by bacteria persisting inside host cells in the lungs (21).…”

Section: Discussionmentioning

confidence: 99%

Tomatidine Inhibits Replication of Staphylococcus aureus Small-Colony Variants in Cystic Fibrosis Airway Epithelial Cells

Mitchell

Gattuso

Grondin

et al. 2011

Antimicrob Agents Chemother

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Small-colony variants (SCVs) often are associated with chronic Staphylococcus aureus infections, such as those encountered by cystic fibrosis (CF) patients. We report here that tomatidine, the aglycon form of the plant secondary metabolite tomatine, has a potent growth inhibitory activity against SCVs (MIC of 0.12 g/ml), whereas the growth of normal S. aureus strains was not significantly altered by tomatidine (MIC, >16 g/ml). The specific action of tomatidine was bacteriostatic for SCVs and was clearly associated with their dysfunctional electron transport system, as the presence of the electron transport inhibitor 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) caused normal S. aureus strains to become susceptible to tomatidine. Inversely, the complementation of SCVs' respiratory deficiency conferred resistance to tomatidine. Tomatidine provoked a general reduction of macromolecular biosynthesis but more specifically affected the incorporation of radiolabeled leucine in proteins of HQNO-treated S. aureus at a concentration corresponding to the MIC against SCVs. Furthermore, tomatidine inhibited the intracellular replication of a clinical SCV in polarized CF-like epithelial cells. Our results suggest that tomatidine eventually will find some use in combination therapy with other traditional antibiotics to eliminate persistent forms of S. aureus.

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Section: Discussionmentioning

confidence: 99%

Tomatidine Inhibits Replication of Staphylococcus aureus Small-Colony Variants in Cystic Fibrosis Airway Epithelial Cells

Mitchell

Gattuso

Grondin

et al. 2011

Antimicrob Agents Chemother

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“…These DNA-based molecular methodologies, which will be examined extensively in this review, include pulsed-field gel electrophoresis (PFGE) and other restriction-based methods, plasmid analysis, and PCR-based typing methods. The incorporation of molecular methods for typing of nosocomial patho-gens has assisted in efforts to obtain a more fundamental assessment of strain interrelationship (1,7,8,55,82,103,(105)(106)(107)(108)(109)(110)(111)138). Establishing clonality of pathogens can aid in the identification of the source (environmental or personnel) of organisms, distinguish infectious from noninfectious strains, and distinguish relapse from reinfection.…”

Section: Introductionmentioning

confidence: 99%

Application of Molecular Techniques to the Study of Hospital Infection

et al. 2006

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SUMMARY Nosocomial infections are an important source of morbidity and mortality in hospital settings, afflicting an estimated 2 million patients in United States each year. This number represents up to 5% of hospitalized patients and results in an estimated 88,000 deaths and 4.5 billion dollars in excess health care costs. Increasingly, hospital-acquired infections with multidrug-resistant pathogens represent a major problem in patients. Understanding pathogen relatedness is essential for determining the epidemiology of nosocomial infections and aiding in the design of rational pathogen control methods. The role of pathogen typing is to determine whether epidemiologically related isolates are also genetically related. To determine molecular relatedness of isolates for epidemiologic investigation, new technologies based on DNA, or molecular analysis, are methods of choice. These DNA-based molecular methodologies include pulsed-field gel electrophoresis (PFGE), PCR-based typing methods, and multilocus sequence analysis. Establishing clonality of pathogens can aid in the identification of the source (environmental or personnel) of organisms, distinguish infectious from noninfectious strains, and distinguish relapse from reinfection. The integration of molecular typing with conventional hospital epidemiologic surveillance has been proven to be cost-effective due to the associated reduction in the number of nosocomial infections. Cost-effectiveness is maximized through the collaboration of the laboratory, through epidemiologic typing, and the infection control department during epidemiologic investigations.

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“…It is well known that Staphylococcus aureus is an initial and chronic colonizer of the mucus gel present in the airways of patients with cystic fibrosis (CF) (Burns & May, 1968;Goerging et al, 1990;Marks, 1990). Bauernfeind et al (1987) reported a longitudinal study of sputa from 102 patients with CF in which the incidence of S. aureus and S. epidermidis was approximately 36 %.…”

Section: Introductionmentioning

confidence: 99%

Calcium- and Mucin-Binding Proteins of Staphylococci

Thomas

Sanford

Ramsay

1993

Journal of General Microbiology

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The association of staphylococci with the mucus gel that overlays the mucosa of the respiratory tract may lead to clearance of cocci or, in certain conditions such as cystic fibrosis (CF), to colonization. In the present study, a quantitative radioassay was used to study the effect of Ca2+, which is elevated in CF sputa, on the adhesion of 3H-labelled Staphylococcus aureus to submaxillary gland much immobilized in MaxiSorp 96-well, break-apart modules. Ca2+ significantly enhanced the adhesion of S. aureus (five strains) and Staphylococcus epidermidis (four strains). The reaction was specific because adhesion was not enhanced in the presence of Mg2+, Ca2+ + EGTA (a Ca" chelator) or protamine and was not attributable to hydrophobicity of the test strains. Staphylococcal adhesion was significantly (P d 0.005) blocked in the presence of highly sialated and sulphated reagents, which suggests that Ca" binds to the sialic acid and sulphate residues of immobilized mucin. The Ca2+-binding sites on the surface of S. aureus were trypsin-sensitive ; in addition, 12%labelled solubilized S. aureus surface proteins reacted with immobilized mucin in a direct binding assay, and the reaction was significantly enhanced by Ca2+. Autoradiography demonstrated that 45Ca bound directly to two polypeptides (M, 170000 and 150000) of solubilized staphylococcal surface proteins separated by SDS-PAGE, and that '251-labelled mucin bound directly to three staphylococcal polypeptides (M, 40000,35000, and 29000). These results suggest that S. aureus adhesion to mucin is mediated by at least two mechanisms: via Ca2+-binding surface proteins in the presence of Ca2+ and via mucin-binding surface proteins unrelated to Ca2+.

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Staphylococcus aureus in patients with cystic fibrosis: An epidemiological analysis using a combination of traditional and molecular methods

Cited by 22 publications

References 11 publications

Tomatidine Inhibits Replication of Staphylococcus aureus Small-Colony Variants in Cystic Fibrosis Airway Epithelial Cells

Tomatidine Inhibits Replication of Staphylococcus aureus Small-Colony Variants in Cystic Fibrosis Airway Epithelial Cells

Application of Molecular Techniques to the Study of Hospital Infection

Calcium- and Mucin-Binding Proteins of Staphylococci

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