Targeting the host–pathogen interface for treatment of Staphylococcus aureus infection

Abstract

Recent emergence of methicillin-resistant Staphylococcus aureus both within and outside healthcare settings has accelerated the use of once reserved last line antibiotics such as vancomycin. With increased use of antibiotics, there has been a rapid rise in the rate of resistance development to the anti-MRSA drugs. As the antibiotic pipeline becomes strained, alternative strategies are being sought for future treatment of S. aureus. Here, we review several novel anti-staphylococcal strategies that, unlike conventional antibiotics, do not target essential gene products elaborated by the pathogen. The approaches seek instead to weaken the S. aureus defense by neutralizing its virulence factors or boosting host immunity. Other strategies target commensal bacteria that naturally colonize the human host to inhibit S. aureus colonization. Ultimately, the aim is to shift the balance between host defense and pathogen virulence in favor of inhibition of S. aureus pathogenic activities.

Genomic Heterogeneity of Methicillin Resistant Staphylococcus aureus Associated with Variation in Severity of Illness among Children with Acute Hematogenous Osteomyelitis

“…Some evidence suggests an association between bacterial strains which express Panton Valentine leukocidin (PVL) and severe complications, such as deep venous thrombosis and septic pulmonary emboli [5,7,27]. However, there is limited direct evidence of the role of single virulence determinants in the pathogenesis of virulent strains [37]. The redundancy of bacterial genes coding for leukocyte defense and the presence of PVL in non-virulent strains imply a more complex cascade of events than that which is explained by the activity of an isolated virulence gene [34,37].…”

“…However, there is limited direct evidence of the role of single virulence determinants in the pathogenesis of virulent strains [37]. The redundancy of bacterial genes coding for leukocyte defense and the presence of PVL in non-virulent strains imply a more complex cascade of events than that which is explained by the activity of an isolated virulence gene [34,37]. In support of this, one group of investigators evaluated 33 putative virulence factors in bacterial isolates from individuals with either invasive or non-invasive S .…”

ω-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation

“…ue to the widespread and seemingly inevitable development of bacterial resistance to antibiotics shortly after their introduction, there is a great need for alternatives or adjuncts to classical antimicrobials (1)(2)(3). Along with ongoing efforts to identify novel antibacterial targets, interventions that are not directly bactericidal may prove efficacious.…”

“…Along with ongoing efforts to identify novel antibacterial targets, interventions that are not directly bactericidal may prove efficacious. These include approaches aimed at modifying or augmenting the host response, as well as approaches that inhibit bacterial virulence mechanisms and thus limit pathogenesis (1)(2)(3). Many pathogenic bacteria coordinate the expression of virulence factors important for invasive infection and pathogenesis through a density-dependent communication system called quorum sensing (QS) (4,5).…”

Investigating the Therapeutic Potential of a Probiotic in a Rat Model for Infection Following Fracture Fixation

“…S. aureus is the most common pathogen responsible for both acute and chronic forms of osteomyelitis (1,5,6). S. aureus has developed a plethora of strategies to evade the host innate and adaptive immune systems, with a high resistance to different therapeutic options (7). Tice et al in a long-term follow-up study of osteomyelitis treated in the outpatient setting found that 31% of 452 patients had recurrent infection, most within one year of occurrence (8).…”