Spontaneous Loss of Virulence in Natural Populations of Listeria monocytogenes
نویسندگان
چکیده
The pathogenesis of Listeria monocytogenes depends on the ability of this bacterium to escape from the phagosome of the host cells via the action of the pore-forming toxin listeriolysin O (LLO). Expression of the LLO-encoding gene (hly) requires the transcriptional activator PrfA, and both hly and prfA genes are essential for L. monocytogenes virulence. Here, we used the hemolytic activity of LLO as a phenotypic marker to screen for spontaneous virulence-attenuating mutations in L. monocytogenes Sixty nonhemolytic isolates were identified among a collection of 57,820 confirmed L. monocytogenes strains isolated from a variety of sources (0.1%). In most cases (56/60; 93.3%), the nonhemolytic phenotype resulted from nonsense, missense, or frameshift mutations in prfA Five strains carried hly mutations leading to a single amino acid substitution (G299V) or a premature stop codon causing strong virulence attenuation in mice. In one strain, both hly and gshF (encoding a glutathione synthase required for full PrfA activity) were missing due to genomic rearrangements likely caused by a transposable element. The PrfA/LLO loss-of-function (PrfA-/LLO-) mutants belonged to phylogenetically diverse clades of L. monocytogenes, and most were identified among nonclinical strains (57/60). Consistent with the rare occurrence of loss-of-virulence mutations, we show that prfA and hly are under purifying selection. Although occurring at a low frequency, PrfA-/LLO- mutational events in L. monocytogenes lead to niche restriction and open an evolutionary path for obligate saprophytism in this facultative intracellular pathogen.
منابع مشابه
Distribution and Characterization of Dominant Serovars of Listeria monocytogenes Strains Isolated from Spontaneous Human Abortion in Tehran
Background and Aims: The aim was to determine the role of dominant serovars of Listeria monocytogenes (L. monocytogenes) in spontaneous abortions, using isolation methods and polymerase change reaction (PCR). Materials and Methods: A total of 258 samples comprising of placental tissue, vaginal swabs and blood were collected from 123 patients with spontaneous abortion. L. monocytogenes was iden...
متن کاملListeriolysin as a virulence factor in Listeria monocytogenes infection of neonatal mice and murine decidual tissue.
Listeriolysin is a 60-kDa protein which allows the growth of Listeria monocytogenes in macrophages and other cells and has been shown to be a virulence factor in Listeria infections of adult mice. However, the neonate and fetoplacental unit are major populations susceptible to listeriosis. Recent data indicate that macrophage and T-cell functions are markedly inhibited in these young mice, and ...
متن کاملIsolation of Listeria monocytogenes from Meat and Dairy Products
Introduction: This study was intended to determine the presence and distribution of Listeria monocytogenes in various meat and dairy products from Qazvin Province by culture followed by biochemical and morphological assays. The identity of the isolates was further obtained by amplification of prfA gene in bacteria isolates. This gene is a transcriptional activator of virulence gene ex...
متن کاملVirulence testing of Listeria monocytogenes.
A major problem in understanding foodborne listeriosis from both the basic science and regulatory perspectives revolves around the role played by virulence factors of Listeria monocytogenes and how these interact with host susceptibility to result in the observed incidence of disease. From a mechanistic perspective, this problem has been well investigated, and many virulence components of L. mo...
متن کامل