Impact of Staphylococcus aureus on the pathogenesis of chronic cystic fibrosis lung disease

Kahl, Barbara C.

doi:10.1016/j.ijmm.2010.08.002

Cited by 78 publications

(56 citation statements)

References 54 publications

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“…For this purpose, we targeted measuring the growth rate of Staphylococcus aureus in CF sputum as a proof of principle. Although CF infections are polymicrobial and compositionally diverse, some bacterial species are common (16). S. aureus is one of the earliest and most prevalent bacteria detected in infants and children with CF, and has garnered attention in the last decade due to the rise of beta-lactam-resistant strains (methicillinresistant S. aureus, or MRSA) (17).…”

Section: Utility Of Highly Sensitive Stable Isotope Tracers For Applimentioning

confidence: 99%

Trace incorporation of heavy water reveals slow and heterogeneous pathogen growth rates in cystic fibrosis sputum

Kopf

Sessions

Cowley

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

111

150

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Effective treatment for chronic infections is undermined by a significant gap in understanding of the physiological state of pathogens at the site of infection. Chronic pulmonary infections are responsible for the morbidity and mortality of millions of immunocompromised individuals worldwide, yet drugs that are successful in laboratory culture are far less effective against pathogen populations persisting in vivo. Laboratory models, upon which preclinical development of new drugs is based, can only replicate host conditions when we understand the metabolic state of the pathogens and the degree of heterogeneity within the population. In this study, we measured the anabolic activity of the pathogen Staphylococcus aureus directly in the sputum of pediatric patients with cystic fibrosis (CF), by combining the high sensitivity of isotope ratio mass spectrometry with a heavy water labeling approach to capture the full range of in situ growth rates. Our results reveal S. aureus generation times with a median of 2.1 d, with extensive growth rate heterogeneity at the single-cell level. These growth rates are far below the detection limit of previous estimates of CF pathogen growth rates, and the rates are slowest in acutely sick patients undergoing pulmonary exacerbations; nevertheless, they are accessible to experimental replication within laboratory models. Treatment regimens that include specific antibiotics (vancomycin, piperacillin/tazobactam, tobramycin) further appear to correlate with slow growth of S. aureus on average, but follow-up longitudinal studies must be performed to determine whether this effect holds for individual patients.slow growth | infectious disease | metabolic heterogeneity | cystic fibrosis | hydrogen isotope labeling

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Section: Utility Of Highly Sensitive Stable Isotope Tracers For Applimentioning

confidence: 99%

Trace incorporation of heavy water reveals slow and heterogeneous pathogen growth rates in cystic fibrosis sputum

Kopf

Sessions

Cowley

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

111

150

View full text Add to dashboard Cite

show abstract

“…[6,7] Persistent MRSA infections represent a new threat to the CF community, as they are not only difficult to treat but are also associated with biofilm formation, Panton-Valentine leukocidin (PVL) production, as well as decreased lung function and patient survival. [8] As respiratory failure continues to be the most common cause of death in CF, appropriate antibiotic treatment constitutes a major challenge for the future development of new active agents against multidrug-resistant MRSA strains.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Agents and Cystic Fibrosis: Synthesis and Antimicrobial Evaluation of a Series of N‐Thiomethylazetidinones

et al. 2011

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The increasing emergence of multidrug-resistant microorganisms is one of the greatest challenges in the clinical management of infectious disease. New antimicrobial agents are therefore urgently required, particularly in the treatment of chronic and recurrent infections often associated with antibiotic-resistant pathogens, as in the case of cystic fibrosis (CF) patients. This study reports the antibacterial activity of a series of monocyclic β-lactams with an alkylidenecarboxyl chain or electron-withdrawing groups such as 4-OAc, 4-SAc, and 4-SO(2)Ph at the C4 position of the ring. N-Unsubstituted and N-thiomethyl derivatives were compared. A total of 33 azetidinones were tested for their activity against Gram-positive and Gram-negative bacterial clinical isolates. The combination of an N-thiomethyl group and a benzyl ester on the 4-alkylidene side chain were found to increase the potency against Gram-positive bacteria. The N-thiomethyl group clearly elevated the activity of 4-acetoxyazetidinones relative to the corresponding NH derivatives. The most active compounds showed minimum inhibitory concentration (MIC) values of 4 and 8 mg L(-1) against methicillin-resistant Staphylococcus aureus isolated from pediatric patients with CF.

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“…While S. aureus is considered a commensal bacterium, as it is a common colonizer of the human skin and respiratory tract, it is also a frequent cause of clinically important infections (Wertheim et al, 2005). In many cases S. aureus is the earliest colonizer in CF patients, and is the most prevalent CF pathogen in children and adolescents (Kahl, 2010;Souza et al, 2006). First elucidating the impact of physiologically relevant concentrations of bile exposure on this important paediatric pathogen, we focused on antibiotic tolerance and biofilm formation.…”

Section: Introductionmentioning

confidence: 99%

Dissecting the regulation of bile-induced biofilm formation in Staphylococcus aureus

et al. 2016

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Impact of Staphylococcus aureus on the pathogenesis of chronic cystic fibrosis lung disease

Cited by 78 publications

References 54 publications

Trace incorporation of heavy water reveals slow and heterogeneous pathogen growth rates in cystic fibrosis sputum

Trace incorporation of heavy water reveals slow and heterogeneous pathogen growth rates in cystic fibrosis sputum

Antibacterial Agents and Cystic Fibrosis: Synthesis and Antimicrobial Evaluation of a Series of N‐Thiomethylazetidinones

Dissecting the regulation of bile-induced biofilm formation in Staphylococcus aureus

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