New role for human ?-defensin 5 in the fight against hypervirulent Clostridium
difficile strains
#MMPMID25547793
Furci L
; Baldan R
; Bianchini V
; Trovato A
; Ossi C
; Cichero P
; Cirillo DM
Infect Immun
2015[Mar]; 83
(3
): 986-95
PMID25547793
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Clostridium difficile infection (CDI), one of the most common hospital-acquired
infections, is increasing in incidence and severity with the emergence and
diffusion of hypervirulent strains. CDI is precipitated by antibiotic treatment
that destroys the equilibrium of the gut microbiota. Human ?-defensin 5 (HD5),
the most abundant enteric antimicrobial peptide, is a key regulator of gut
microbiota homeostasis, yet it is still unknown if C. difficile, which
successfully evades killing by other host microbicidal peptides, is susceptible
to HD5. We evaluated, by means of viability assay, fluorescence-activated cell
sorter (FACS) analysis, and electron microscopy, the antimicrobial activities of
?-defensins 1 and 5 against a panel of C. difficile strains encompassing the most
prevalent epidemic and hypervirulent PCR ribotypes in Europe (012, 014/020, 106,
018, 027, and 078). Here we show that (i) concentrations of HD5 within the
intestinal physiological range produced massive C. difficile cell killing; (ii)
HD5 bactericidal activity was mediated by membrane depolarization and bacterial
fragmentation with a pattern of damage peculiar to C. difficile bacilli, compared
to commensals like Escherichia coli and Enterococcus faecalis; and (iii)
unexpectedly, hypervirulent ribotypes were among the most susceptible to both
defensins. These results support the notion that HD5, naturally present at very
high concentrations in the mucosa of the small intestine, could indeed control
the very early steps of CDI by killing C. difficile bacilli at their germination
site. As a consequence, HD5 can be regarded as a good candidate for the
containment of hypervirulent C. difficile strains, and it could be exploited in
the therapy of CDI and relapsing C. difficile-associated disease.
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