Virulence Factor Activity Relationships: Challenges and Development Approaches

Abstract

Virulence factor activity relationships (VFAR) is a predictive approach proposed by the National Research Council's Committee on Drinking Water Contaminants (Washington, D.C.) to classify and rank waterborne pathogens. It is based on the presumption that health threats of waterborne pathogens can be predicted from descriptors at different levels of cellular organization. This paper summarizes challenges that need to be addressed while developing VFAR, with a focus on genomics, such as genomic variability among related pathogens and the need to incorporate genetic descriptors for persistence and host susceptibility. Three key components of VFAR development and validation are also presented, including (1) compilation of a comprehensive VFAR database, (2) development of predictive mathematical models relating descriptors to health effects and other microbial responses, and (3) high-throughput molecular monitoring of drinking water supplies and sources. Bayesian approach and on-chip polymerase chain reaction are discussed as examples of mathematical models and molecular monitoring. Water Environ. Res., 79, 246 (2007).

Molecular quantification of virulence gene-containing Aeromonas in water samples collected from different drinking water treatment processes

“…Sequence variability of a virulence gene in various pathogens poses a great challenge for the development of real-time PCR and biochip assays to be used for accurate identification and quantification of pathogens in environmental samples (Tourlousse et al 2007). In this study, we observed high Ct values when using Aeromonas isolates to validate the developed real-time PCR assays.…”

“…The National Research Council's Committee on Drinking Water Contaminants (Washington, DC) has recommended a comprehensive approach based on the virulence factor activity relationships as a means to predict potential risks from a wide range of pathogens in drinking water. The needs to know better about the distribution and genetic level of virulence genes of waterborne pathogens are supported by many previous studies (Tourlousse et al 2007;Miller et al 2008). These studies have suggested that relying on only one single virulence gene of pathogenic strains might possibly lead to incorrect assessment of the microbial risk of waterborne diseases because (1) many virulence genes are unevenly distributed among different pathogenic strains, (2) many virulence genes are multifunctional, and (3) some virulence can be even found in nonpathogenic strains.…”

In silico environmental chemical science: properties and processes from statistical and computational modelling

“…[140][141][142][143][144][145] An even greater challenge lies in the extension of QSAR methods to biological properties like virulence (i.e., virulence factor activity relationships, VFARs). [146][147][148] The challenges involved in implementing useful VFARs are considerable, but may eventually succumb to the combination of advances from computational toxicology 1 and omic sciences. 149…”

Virulence factor activity relationships (VFARs): a bioinformatics perspective

“…More often, these developments are based on studies that predate the first VFAR report and do not necessarily use the term – VFAR. In fact, of the more than one hundred publications reviewed here due to their relevance to VFARs, only few 5–8 refer to the original National Research Council report. 1 This exemplifies that the need for developing the ability to predict functions including virulence based on sequence information is universal and includes scientists engaged in predicting increased risk of infectious diseases due to climate change, clinicians engaged in predicting antimicrobial resistance, and regulatory bodies engaged in ensuring public and ecosystem health, among many others.…”