Medical and General microbiology reading notes Flashcards
Eradicating infectious disease: can we and should we?
Only 2 eradicated are smallpox and rinderpest virus, both are viruses as easiest to eradicate through vaccination
Only thing stopping polio being eradicated is social issues rather than biological
Problem with live vaccines such as the oral polio vaccine is that they can revert back to the pathogenic form
Can’t eradicate herpes as lies in neurones where infection can reactivate them
Influenza A is an RNA virus whose antigens are constantly chang- ing due to antigenic shift and drift, so vaccine constantly updated each season
Bacteria represent a bigger problem in that, unlike viruses, few pathogenic bacteria are obligate pathogens. Many are opportun- istic pathogens: these can be members of the normal flora that only cause disease if the host is immunodeficient or they access a normally sterile area.
A further complication of eradication is that many bacteria have animal reservoirs, eg rectum of cattle
Chlamydia eradicable as we are essential in its life cycle
Environmentally can try and eradicate a pathogen eg. via getting rid of contaminated water
Eradication dangerous as affects competition between different bacterias so more dangerous one could become more prominent
Eradication of inequality in health care should be the first step
What is a pathogen? (Liise-anne Pirofski and Arturo Casadevall*)
Usually defined as a micro-organism causes or can cause disease, or damage in a host
Definition in a grey area due to microbes that used to be considered non pathogenic causing disease in immuno compromised people
Antibiotics and surgery make more vulnerable to disease as it disrupts the normal microbial flora especially mucosal
Pathogen is not a pathogen if you are vaccinated as they don’t produce the factors they would in a susceptible host hence making them not a pathogen anymore
pathogenicity is an outcome of host-microbe interaction and is thus inextricably linked to characteristics of the host as well as those of the microbe.
Commensals (also called the microbiota) are acquired by infection soon after birth, after which they establish residence in mucosal niches where they replicate, they also help to develop the immune system
pathogenicity can be due to the immune response to the pathogen rather than the pathogen itself
Pathogenicity is defined
by the capacity of a microbe to cause damage in a (susceptible) host. (discontinuous)
Virulence is defined as the relative capacity of a microbe to cause damage in a host (continuous)
Polybacterial human disease: the ills of social networking? (Francesca L. Short, Sarah L. Murdoch, and Robert P. Ryan)
Polybacterial diseases involve multiple organisms that act collectively to facilitate disease progression
immunization against single virulence factors has proven unsuccessful in many situations, sug- gesting far greater complexity than initially envisaged
This re-evaluation has been driven in recent years by the improvement of diagnostic and genomic technologies
Interspecies communication through diffusible signals aids Polybacterial diseases
Contact-dependent interactions between bacteria during infection aids Polybacterial diseases
quorum sensing = Bacteria of the same species often use signal molecules to monitor aspects of their environment such as population density
Interactions can include commensal bacteria
In addition to antagonistic interactions, different species of bacteria can also act in a cooperative fashion through metabolite cross-feeding, where one species utilizes an end-product of a metabolic pathway of another species.
What are the consequences of the disappearing human microbiota?
Propose the idea that the disappearance of microbiota which have pathogenic properties due to our interference can have negative consequences such as obesity and asthma
Although possibly germ-free (gnotobiotic) before birth, humans develop a resident microbiota shortly after birth.
The human microbiota facilitate the extraction of energy from food, provide accessory growth factors, promote post-natal terminal differentiation of mucosal struc- ture and function, stimulate both the innate and adaptive immune systems,
there seems to be no absolute requirement for a functional resident microbiota, but nor does gnotobiosis occur in nature.and provide ‘colonization resistance’ against pathogen invasion1
Microbiota can cause infection in our body as well if circumstances change
Grey area between a pathogen and a commensal micro-organism which only causes disease in specific situations
Various microorganisms survive in us via Nash equallibrium both sets of micro-organisms know what they are doing to gain advantage but trying to counteract that will only be negative to them. This is what sets up the boundaries
As human health and longevity have improved in developed countries, new diseases have arisen without obvious explanation = disappearing microbiota’ hypothesis
Don’t believe in hygiene hypothesis being main cause, which is the idea that us not sampling germs as naturally anymore is bad for us. Idea that if a species of microbiota is lost in the parents then the child won’t have it and due to better public health they won’t be infected with it naturally
ancestral indigenous microorganism disappeared in the colon, mouth, skin or vagina, could we identify that change and, crucially, could such a change (whether it was a loss or a replacement and subsequent ‘overgrowth’ by a different indigenous com- ponent) contribute to some of the diseases that are becoming more prevalent?
H. pylori-positive individuals (especially individuals carrying cag-positive strains) have lower risks of childhood asthma, allergic rhinitis and skin allergies than those without H. pylori
ecological changes involving our ancient microbiota have the power to affect physiology and, ultimately, health.
we must learn to bet- ter distinguish between pathogens and amphibionts and to better assess in whom to eliminate, leave alone or restore the microorganism (or metabolic pathway) in question
Serogroup B Meningococcus Outbreaks, Prevalence, and the Case for Standard Vaccination
Serogroup B meningitis represents 30% of American meningococcal infections and had no commercially available vaccine in the USA until 2013 when the FDA made an expanded allowance for importation of the MenB-4C vac- cine for outbreaks at two American universities.
2013 The Princeton Outbreak: Nine Cases, One Death, countered with strong campus vaccination
Streptococcus suis infection
An emerging/reemerging challenge of bacterial infectious diseases
Streptococcus suis (S. suis) is a family of pathogenic gram- positive bacterial strains that represents a primary health problem in the swine industry worldwide.
emerging zoonotic pathogen that causes severe human infections clinically featuring with varied diseases/syndromes (such as meningitis, septicemia, and arthritis)
over 20 bacte- rial virulence-associated factors have been identified that include capsular polysaccharides (CPS),20 Muramidase-released protein (MRP),21 and Suilysin (SLY)
S. suis is a group of heterogeneous gram-positive bacteria
facultative anaerobes with a spherical/ovoid shape which exist in pairs and/or short chains
SS2 is recognized as the most virulent species
14 genomes of S. suis strains have been available in PubMed
60 bacterial components have been identi- fied to be involved in the infection and/or pathogenicity of S. suis
(1) sur- face/secreted elements; (2) enzymes/proteases; (3) transcription factors/regulatory systems; and (4) others (transporters/secretion systems)
The role of the microbiome in human health and disease: an introduction for clinicians?
the most radical change is the realization that most of the microbes that inhabit our body supply crucial ecosystem services that benefit the entire host-microbe system.
nclude the production of important resources, bioconversion of nutrients, and protection against pathogenic microbes.
disease can result from a loss of beneficial functions or the introduction of maladaptive functions by invading microbes
Impact of diet-microbiota interactions on human metabolism?
Known fact microbiota can metabolise dietary components
A functional analysis of these microbiomes revealed that an obesity-associated microbiota had an increased capacity for energy harvest, and this phenotype could be transferred through faecal microbiota transplant
Hence the mice with germs were fatter than the others
diet was found to consistently alter the gut microbiota
high-fibre diets that are typically consumed by rural communities were associated with increased microbial diversity, an enrichment of Prevotella species, higher concentrations of health-promoting short-chain fatty acids and a reduction in metabolic disease.
Host defense peptides: An insight into the antimicrobial world?
Antimicrobial peptides (AMPs) have gained importance because of their broad-spectrum antimicrobial activities and mediator-like functions linking innate and adaptive immune responses.
AMPs are oligopeptides that are biologically active molecules produced by different sources including plants, animals, microorganisms and mammals. In humans, AMPs are widely distributed in saliva, epithelium and neutrophils having a broad range of antimicrobial activity and are effective in immune activation, wound healing and inflammation.
AMPs are less toxic and have antimicrobial specificity due to which they kill specific target cells without affecting the host cells; therefore, decreased resistance is developed by target cells against them.
The primary mechanism for antimicrobial activity of AMPs is the electrostatic interaction of peptides with negatively charged molecules on the membrane.
AMPs can also exert antimicrobial activity by cell membrane translocation and inhibition of essential cellular processes including nucleic acid synthesis, cell wall synthesis, protein synthesis and enzymatic activities
MALDI-TOF MS in the Microbiology Laboratory: Current Trends?
Within less than a decade matrix-assisted laser desorption/ionization time-of-flight mass spectro- metry (MALDI-TOF MS) has become a gold standard for microbial identification in clinical microbiology laboratories.
identification of microorganisms the typing of single strains as well as the antibiotic and antimycotic resistance testing has come into focus in order to speed up the microbiological diagnostic.
the full potential of MALDI-TOF MS has not been tapped yet and future technological advancements will certainly expedite this method
Next-Generation Sequencing in Clinical Microbiology: Are We There Yet?
The 3 main applications of next-generation sequencing in clinical microbiology labora- tories include (1) whole-genome sequencing (WGS), (2) targeted next-generation sequencing (tNGS), and (3) metagenomics next-generation sequencing.
WGS is becoming commonplace in public health laboratories, aiding in the rapid identifi- cation and tracking of infectious disease outbreaks alongside detection of emerging resis- tance and surveillance.
tNGS has been underutilized in clinical microbiology; however, the development of new enrichment methods will allow for broad pathogen detection combined with high sensi- tivity. tNGS may become a more accessible assay in the future.
Metagenomic next-generation sequencing has emerged as a promising single, universal pathogen detection (ie, bacteria, fungi, parasites, viruses) method for infectious diseases diagnostics performed directly from clinical specimens. Laboratory-developed tests are now being offered as billable tests; understanding the limitations of these nonstandardized and expensive tests is imperative for appropriate test utilization and result interpretation.
Small Molecules
Sabotage Bacterial Virulence
This approach to treating bacteria-mediated diseases may have advantages over traditional antibiotics because it targets factors specific for pathogenesis, potentially reducing selection for resistance and limiting collateral damage to the resident microbiota
Molecular mechanisms of antibiotic resistance?
Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria.
. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis.
mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.
Autophagic clearance of bacterial pathogens: molecular
recognition of intracellular microorganisms?
Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response
Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments
helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection.
Salmonella–host interactions – modulation of the host innate immune system?
Salmonella enterica (S. enterica) are Gram-negative bacteria that can invade a broad range of hosts causing both acute and chronic infections
This phenotype is related to its ability to replicate and persist within non-phagocytic host epithelial cells as well as phagocytic dendritic cells and macrophages of the innate immune system.
Studies focusing on the host–pathogen interaction have provided insights into receptor activation of the innate immune system.
