Microbial virulence
Objectives:
- define microbial virulence and host susceptability
- revise host defences against infection
- relate virulence to clinical disease
- pseudomonas aeruginosa
Key concepts
- infection is dependent on host susceptibility
- pathogenesis is a process driven by micro virulence
- pathology a result of microbial factor and host responses
Content:
pathogen: microbe which causes infection pathogenicity: ability of a microbe to cause infection virulence: Measure of pathogenicity in a susceptible host virulence factor: gene product that enables better colonization of a susceptible host
susceptability defined: level of vulnerablility of a host to infection factors that increase susceptability:
- age
- comorbidities
- lifestyle
- genetics
- immunization
- medical interventions
- medications
- trauma
- socioeconomic
virulence + susceptability = infection
scenarios normal host virulence = host defences = no infection low virulence from a pathogen but low defences from a host low virulence > low defences = infection high virulence normal defences high virulence > normal defences = infection
infection depends on many things
- microbial factors
- host factors
- enviromental factors (wearing PPE block transmission)
pathology is also multifactoral microbes can damage tissues and cause pathogenesis inappropriate host responses can also cause tissue damage and pathogenesis
dependant on:
- what microbial virulence factors is at play and
- if the host response is regulated
note the cycle of damage where massive response to a pathogen causes further damage which triggers a larger response.
components of susceptability (or strength) intrinsic (nonimmune)
- physical barriesr
- secretions
- physical removal
- pH
- microbiome immune
- innate
- phagocytosis
- inflammation
- pattern recognition
- complement
- cytokines chemokines
- adaptive
- t cells
- b cells
- cytokines
- complement (classical activation)
Medical interventions can disrupt these leading to infection
Microbiome bacteria that live commensally with your body. can contain oppertunistic bacteria
Case study/ example
pseudomonas aerugiosa
- gram negative rod
- 3-5% of perople are colonised (skin, gut)
- 20% of hospital patients are colonised
- hospital acquired infection with significant mortality
- in the envirtoment
clinical diseases caused
- LRTI (CF)
- sepsis
- bone and joint infections
- uti
- eye and ear infections
- localised infections
- folliculitis
it is opportunistic so needs help infecting (iatrogenic, wound, immune dysfunction etc)
virulence factors:
- biofilms and capsules
- motility
- adhesins
- invasins
- affecting host response
- toxins
difficult to treat
- multidrug resistant
- rapidly acquires resistance
- combinations and broad spectrum drugs required
candida albicans (fungi) 50-80% of people are colonised commensal in its yeast form infection in its mould form in healthy people mucocutanous infections can arise in immunocomprimised people systemic invasive infections can arise leading to high mortality Hospital aquired infection
virulence factors:
- attachment
- biofilms
- immune evasion
- enzymes
- antifungal resistance is an emerging challange
influenza a haemagglutinin
- attachment and uptake
- neuraminidase antigenic variation drift shift
virulence is always evolving virulence genes may be on mobile genetic elements plasmids transposons and pahges bacteria readily take up MGE antimicrobial resistance is spreading
Summary
• Virulence is a measure of pathogenicity or ability to cause disease
• Virulence factors are gene products produced by microbes to colonize host
– Adhesins, toxins, enzymes, immune evasion, biofilms, capsules
• Infection arises when these factors are expressed in a susceptible host
– Host susceptibility important
– Susceptible hosts common in healthcare setting
– Host response determines severity of disease
– Pathology dependent on microbe & host factors
Virulent microbe
Susceptible host
=
Infection
• Fungi & viruses (& parasites) use similar strategies to cause disease
• Virulence factors are encoded on MGE & readily transmissible
– Antimicrobial resistance is a major concern
– Appropriate use/prescription important in controlling spread of resistance
• Antimicrobial stewardship