Bacterial virulence as a target for antimicrobial chemotherapy

Alksne, Lefa; Projan, Steven J.

doi:10.1016/s0958-1669(00)00155-5

Cited by 151 publications

(98 citation statements)

References 116 publications

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“…Distinction between these phenotypes is crucial, because the underlying molecular factors may be entirely different, especially in the case of S. aureus, which may colonize humans in an asymptomatic fashion. Notably, the analysis of virulence potential is a key prerequisite for endeavors to find anti-CA-MRSA therapeutics, particularly those that use modern target-oriented drug development (36). Therefore, in an effort to establish a scientific basis for drug development against CA-MRSA, we focused on the evolution of virulence within CC8.…”

Section: Discussionmentioning

confidence: 99%

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Diep

Villaruz

et al. 2009

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

362

373

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Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged worldwide. The United States, in particular, is experiencing a serious epidemic of CA-MRSA that is almost entirely caused by an extraordinarily infectious strain named USA300. However, the molecular determinants underlying the pathogenic success of CA-MRSA are mostly unknown. To gain insight into the evolution of the exceptional potential of USA300 to cause disease, we compared the phylogeny and virulence of USA300 with that of closely related MRSA clones. We discovered that the sublineage from which USA300 evolved is characterized by a phenotype of high virulence that is clearly distinct from other MRSA strains. Namely, USA300 and its progenitor, USA500, had high virulence in animal infection models and the capacity to evade innate host defense mechanisms. Furthermore, our results indicate that increased virulence in the USA300/USA500 sublineage is attributable to differential expression of core genome-encoded virulence determinants, such as phenol-soluble modulins and ␣-toxin. Notably, the fact that the virulence phenotype of USA300 was already established in its progenitor indicates that acquisition of mobile genetic elements has played a limited role in the evolution of USA300 virulence and points to a possibly different role of those elements. Thus, our results highlight the importance of differential gene expression in the evolution of USA300 virulence. This finding calls for a profound revision of our notion about CA-MRSA pathogenesis at the molecular level and has important implications for design of therapeutics directed against CA-MRSA.

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Section: Discussionmentioning

confidence: 99%

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Diep

Villaruz

et al. 2009

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

362

373

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“…More recently, specifically targeting virulence rather than essential fungal processes has been discussed as a 'new' paradigm for the development of antibacterial and antifungal agents [74,75]. The modulation of morphogenesis may provide a way to specifically target virulence of C. albicans [76].…”

Section: Is Inhibition Of the Yeast-to-hyphal Transition A Therapeutimentioning

confidence: 99%

Candida albicansdimorphism as a therapeutic target

Jacobsen

Wilson

Wachtler

et al. 2012

Expert Review of Anti-infective Therapy

321

247

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“…AIP then accumulates in the environment by increased expression of the communication signal, or by increased numbers of cells producing the signal. Once the AIP reaches a threshold concentration, it interacts with a cell-surface receptor or reenters the cell and causes a cascade of transcriptional regulation (Alksne and Projan, 2000).…”

Section: E Faecalis and Biofilim Formationmentioning

confidence: 99%

Enterococcus faecalis, a nightmare to endodontist: A systematic review

John¹,

Kumar²,

Gopal³

et al. 2015

Afr. J. Microbiol. Res.

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The main goal in endodontics is the prevention and treatment of diseases of the dental pulp and periapical tissues and it can be best achieved if preventive measures and treatment procedures are based on a thorough and detailed understanding of the etiology and pathogenesis of endodontic diseases. There are some cases in which the treatment has followed the highest technical standards and yet failure results. Scientific evidence indicates microbial factors which play an important role. In most cases, failure of endodontic treatment is a result of microorganisms persisting in the apical portion of the root canal system, even in well-treated teeth. Enterococcus faecalis is recognized as a pathogen in posttreatment endodontic infections and probably the species that can best adapt to and tolerate the ecologically demanding conditions in the filled root canal. Enterococci are also implicated in infections of the root canal system, however, they make up a small proportion of the initial flora which is dominated by Gram negative species. In contrast, it has been reported that enterococci are frequently isolated from obturated root canals of teeth that exhibit chronic periapical pathology. Eradication of E. faecalis from the root canal remains a challenge, while chlorhexidine and combinations of disinfectants show some promise. A better understanding of the role of the virulence factors of E. faecalis in endodontic infections may help in the development of new strategies to prevent or eliminate the infection by this species, thereby improving treatment results in endodontics.

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Bacterial virulence as a target for antimicrobial chemotherapy

Cited by 151 publications

References 116 publications

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus

Candida albicansdimorphism as a therapeutic target

Enterococcus faecalis, a nightmare to endodontist: A systematic review

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