Pathogenicity and virulence

Invertebrate pathologists have multiple definitions for the terms pathogenicity and virulence, and these definitions vary across disciplines that focus on host-pathogen interactions. We surveyed various literatures, including plant pathology, invertebrate pathology, evolutionary biology, and medicine, and found most define pathogenicity as the broader term, which incorporates virulence. Virulence is seen as the severity of disease manifestation that can only be measured in infected individuals. These definitions readily apply to both lethal and non-lethal diseases. Invertebrate pathologists commonly use dose-response bioassays to estimate LD(50) or LC(50) (dose or concentration needed to kill 50% of hosts exposed). These bioassays measure pathogenicity if the bioassay includes a transmission component, and measure virulence if the bioassay is measured in infected individuals only. Another common bioassay estimate is LT(50) (median time to death of infected hosts), which is a measure of virulence as long as survivors are not included in its calculation.     

Parasitoid wasp virulence

In nature, larvae of the fruit fly Drosophila melanogaster are commonly infected by parasitoid wasps. Following infection, flies mount an immune response termed cellular encapsulation in which fly immune cells form a multilayered capsule that covers and kills the wasp egg. Parasitoids have thus evolved virulence factors to suppress cellular encapsulation. To uncover the molecular mechanisms underlying the antiwasp response, we and others have begun identifying and functionally characterizing these virulence factors. Our recent work on the Drosophila parasitoid Ganaspis sp.1 has demonstrated that a virulence factor encoding a SERCA-type calcium pump plays an important role in Ganaspis sp.1 virulence. This venom SERCA antagonizes fly immune cell calcium signaling and thereby prevents the activation of the encapsulation response. In this way, the study of wasp virulence factors has revealed a novel aspect of fly immunity, namely a role for calcium signaling in fly immune cell activation, which is conserved with human immunity, again illustrating the marked conservation between fly and mammalian immune responses. Our findings demonstrate that the cellular encapsulation response can serve as a model of immune cell function and can also provide valuable insight into basic cell biological processes.     

Molecular analysis of spv virulence genes of the salmonella virulence plasmids

Genes on an 8 kb region common to the virulence plasmids of several serovars of Salmonella are sufficient to replace the entire plasmid in enabling systemic infection in animal models. This virulence region encompasses five genes which previously have been designated with different names from each investigating laboratory. A common nomenclature has been devised for the five genes, i.e. spv for s almonella p lasmid v irulence. The first gene, spvR, encodes a positive activator for the following four genes, spvABCD. DNA sequence analysis of the spv genes from Salmonella typhimurium. Salmonella dublin, and Salmonella choleraesuis demonstrated extremely high conservation of the DNA and amino acid sequences. The spv genes are induced at stationary phase and in carbon-poor media, and optimal expression is dependent on the katF locus. The cirulence functions of the spv genes are not known, but these genes may increase the growth rate of salmonellae in host cells and affect the interaction of salmonellae with the host immune system.     

The ecology of virulence

Theoretical work has shown that parasites should evolve intermediate levels of virulence. Less attention has been given to the ecology of virulence. Here I explore population-dynamic models of infection in an annual host. The infection does not kill the host; but it can decrease the number of offspring produced by the host, and the magnitude of this effect depends on host population size. Hence, 'virulence' is density dependent, and is defined here as the difference in birth rates between uninfected and infected hosts, divided by the birth rate of uninfected hosts. The results suggest that infection can be highly virulent at the host's equilibrium density, even though the parasite has no effect on the host's intrinsic birth rate. The results also suggest that parasites may help to stabilize host population dynamics. In general, the impact of infection may be underestimated in natural populations.     

Chromatin-mediated Candida albicans virulence

Candida albicans is the most prevalent human fungal pathogen. To successfully propagate an infection, this organism relies on the ability to change morphology, express virulence-associated genes and resist DNA damage caused by the host immune system. Many of these events involve chromatin alterations that are crucial for virulence. This review will focus on the studies that have been conducted on how chromatin function affects pathogenicity of C. albicans and other fungi. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.     

MRSA virulence and spread

Methicillin‐resistant Staphylococcus aureus (MRSA) is one of the most frequent causes of hospital‐ and community‐associated infections. Resistance to the entire class of β‐lactam antibiotics, such as methicillin and penicillin, makes MRSA infections difficult to treat. Hospital‐associated MRSA strains are often multi‐drug‐resistant, leaving only lower efficiency drugs such as vancomycin as treatments options. Like many other S. aureus strains, MRSA strains produce a series of virulence factors, such as toxins and adhesion proteins. Recent findings have shed some new light on the molecular events that underlie MRSA epidemic waves. Newly emerging MRSA clones appear to have acquired phenotypic traits that render them more virulent or able to colonize better, either via mobile genetic elements or via adaptation of gene expression. Acquisition of Panton‐Valentine leukocidin genes and increased expression of core genome‐encoded toxins are being discussed as potentially contributing to the success of the recently emerged community‐associated MRSA strains. However, the molecular factors underlying the spread of hospital‐ and community‐associated MRSA strains are still far from being completely understood, a situation calling for enhanced research efforts in that area.     

Correlation between the distribution pattern of virulence genes and virulence of Aeromonas hydrophila strains

Nine strains of Aeromonas hydrophila isolated from diseased fish or soft-shelled tortoise were tested for the presence of three virulence genes including the genes encoding aerolysin,hemolysin,and extracellular serine protease (i.e.,aerA,hlyA,and ahpA,respectively).These genes were investigated using polymerase chain reaction (PCR)with specific primers for each gene.And the pathogenicities to Carrassius auratus ibebio of these strains were also assayed.PCR results demonstrated that the distribution patterns of aerA,hlyA,and ahpA were different in these strains.6/9 of A.hydrophila strains were aer A positive,8/9 of strains hly A positive,7/9 of strains ahp A positive,respectively.However,the assay for pathogenesis showed that two strains (A.hydrophila XS91-4-1 and C2)were strong virulent,two strains (A.hydrophila ST78-3-3 and 58-20-9)avirulent and the rest middle virulent was to the fish.In conclusion,there are significant correlation between the distribution pattern of the three virulence genes and the pathogenicity to Carrassius auratus ibebio.All strong virulent A.hydrophila strains were aerA+hlyA+ahpA+genotype,and all aerA+hlyA+ahpA+strains were virulent.Strains with the genotype of aerA-hlyA-ahpA+have middle pathogenicity.In the present study,we found for the first time that all A.hydrophila isolated from the ahpA positive were virulent to Carrassius auratus ibebio.Additionally,there was a positive correlation between the virulence of A.hydrophila and the presence of aerA and ahpA.     

Dismantling the bacterial virulence program

In the face of rising antimicrobial resistance, there is an urgent need for the development of efficient and effective anti-infective compounds. Adaptive resistance, a reversible bacterial phenotype characterized by the ability to surmount antibiotic challenge without mutation, is triggered to cope in situ with several stressors and is very common clinically. Thus, it is important to target stress-response effectors that contribute to in vivo adaptations and associated lifestyles such as biofilm formation. Interfering with these proteins should provide a means of dismantling bacterial virulence for treating infectious diseases, in combination with conventional antibiotics.