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Published on: April 2, 2013
The Leeuwenhoek Lecture, 1991. The influence of the host on microbes that cause disease
1Medical School, University of Birmingham, U.K.
Abstract:
Microbial pathogenicity or virulence, the capacity to cause disease, depends on microbial gene products that promote infection and penetration of mucous membranes, multiplication in the tissues, interference with host defence and sickness. Formation of these virulence determinants by microbes is influenced by the environment of the host, which differs from that in laboratory cultures. Studies of microorganisms grown in vivo, and of the host's influence on the production of virulence determinants, are increasing. In most studies, however, the complex conditions in vivo are not dissected to show the influence of particular factors. In future we should define specific host factors that are responsible for producing identified virulence determinants. There are three studies which point the way. Iron limitation in vivo causes production of bacterial siderophores, outer membrane receptors and some toxins. Erythritol, a growth stimulant for brucellae, causes intense placentitis and hence abortion in cattle, sheep and pigs. Cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA) sialylates a conserved component of gonococcal lipopolysaccharide (LPS), thereby rendering gonococci in patients resistant to complement-mediated killing by serum. Although the lecture uses bacteria for examples, the principle applies equally to studies of viral and fungal pathogenicity.
Insights
Microbial virulence, the ability to cause disease, is shaped by host environments, not just lab conditions. Understanding specific host factors is key to controlling infections and developing new treatments.
Area of Science:
- Microbiology
- Pathogenesis
- Host-Pathogen Interactions
Background:
- Microbial pathogenicity, or virulence, is the capacity to cause disease.
- Virulence depends on microbial gene products that facilitate infection, multiplication, and host defense interference.
- Microbial gene product formation is influenced by the host's in vivo environment, which differs from laboratory cultures.
Purpose of the Study:
- To highlight the increasing importance of studying microorganisms grown in vivo.
- To emphasize the need to dissect complex in vivo conditions to understand specific host factor influences on virulence determinant production.
- To identify specific host factors responsible for producing identified virulence determinants.
Main Methods:
- Review of studies investigating microbial growth and virulence factor production in vivo.
- Analysis of specific host-derived factors influencing microbial virulence, including iron limitation, erythritol, and CMP-NANA.
- Examination of how these factors impact microbial survival and pathogenicity.
Main Results:
- Iron limitation in vivo induces bacterial siderophores, outer membrane receptors, and toxins.
- Erythritol acts as a growth stimulant for brucellae, leading to placentitis and abortion in livestock.
- CMP-NANA modifies gonococcal lipopolysaccharide (LPS), conferring resistance to complement-mediated killing.
Conclusions:
- Specific host factors significantly influence microbial virulence determinant production.
- Understanding these host-pathogen interactions is crucial for controlling infectious diseases.
- The principles discussed apply to bacterial, viral, and fungal pathogenicity.
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