CRH Affects the Phenotypic Expression of Sepsis-Associated Virulence Factors by Streptococcus pneumoniae Serotype 1 In vitro

Abstract

Sepsis is a life-threatening health condition caused by infectious pathogens of the respiratory tract, and accounts for 28–50% of annual deaths in the US alone. Current treatment regimen advocates the use of corticosteroids as adjunct treatment with antibiotics, for their broad inhibitory effect on the activity and production of pro-inflammatory mediators. However, despite their use, corticosteroids have not proven to be able to reverse the death incidence among septic patients. We have previously demonstrated the potential for neuroendocrine factors to directly influence Streptococcus pneumoniae virulence, which may in turn mediate disease outcome leading to sepsis and septic shock. The current study investigated the role of Corticotropin-releasing hormone (CRH) in mediating key markers of pneumococcal virulence as important phenotypic determinants of sepsis and septic shock risks. In vitro cultures of serotype 1 pneumococcal strain with CRH promoted growth rate, increased capsule thickness and penicillin resistance, as well as induced pneumolysin gene expression. These results thus provide significant insights of CRH–pathogen interactions useful in understanding the underlying mechanisms of neuroendocrine factor's role in the onset of community acquired pneumonias (CAP), sepsis and septic shock.

Mammalian Neuropeptides as Modulators of Microbial Infections: Their Dual Role in Defense versus Virulence and Pathogenesis

“…This was evident for serotypes 1, 3, 19A and 23F, among the major causes of invasive pneumococcal disease. Furthermore, CRH-treated bacteria presented 3-fold greater resistivity for penicillin/streptomycin cocktail compared to control [ 45 ]. Since capsules generally act as an armor, that prevents complement-dependent cell lysis and C3b- or IgG-dependent opsonization that leads to phagocytosis enhancement [ 54 ], it is reasonable to suggest that CRH may make it harder for the phagocytic cell to recognize and phagocytize this encapsulated pathogen.…”

“…Proteolytic degradation of neuropeptides by microbial proteases, however, seems to be a different and more likely matter. The findings that various bacteria such as P. aeruginosa , E. faecalis , Proteus mirabilis , S. enterica , S. pyogenes , Burkholderia cenocepacia , Vibrio cholera and pathogenic yeasts such as C. albicans can cleave pivotal antimicrobial peptides including LL-37 appear to support this notion [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 …”