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Signal transduction
- Transmission of information from outside cell to inside
- Allows cells to monitor and react to environmental conditions
Quorum Sensing
Allows some organisms to "sense" density of their own population
Two Component Regulatory System: what proteins are used?
Membrane-spanning sensor and Response regulator
Membrane-spanning sensor
- Modifies internal region in response to specific environmental variations
- Phosphorylates amino acid
Response regulator
- Phosphate group transferred from sensor
- Regulator turns genes on or off
Example of Two Component Regulatory System
- pathogen sensing magnesium levels to recognize presence in host cell
Antigenic variation
alteration of characteristics of surface proteins
Phase variation
switching genes on and off
first genome published
Haemophilus influenzae
Data interpretation is complex due to:
Promoter orientation
Which DNA strand is template
Reading frame
Metagenomics
Analysis of total microbial genomes in environment
Metagenomics can be used to
track changes in composition of microbiota of individual over time (healthy, diseased)
Horizontal Gene Transfer
Microorganisms acquire genes from other cells by horizontal gene transfer (HGT)
Bacterial Transformation
"naked" DNA taken up from the environment
Transduction
bacterial DNA transfer by a virus
Conjugation
DNA transfer during cell-to-cell contact 12
Homologous recombination
Donor DNA replaces complementary region of recipient cell's DNA
Bacterial Transformation is also known as
DNA-mediated transformation
Transduction
transfer of bacterial genes by bacteriophages(phages)
Generalized transduction
results when a fragment of bacterial DNA enters the phage protein coat
- produces transducing particle
Transducing particle may
attach to another bacterial cell and inject the DNA it contains
Conjugative plasmids
direct their own transfer
F+ cells contain
F plasmid
F- cells do not contain
F plasmid
Hfr cells
high frequency of recombination
F′ plasmid results when
small piece of chromosome is removed with F plasmid DNA
pan-genome
consists of 3 sets of genes
Core genome
common to all strains
accessory genome
present in more than one but not all strains
Unique genes
found in only one strain of the species
Mobile genetic elements
can move from one DNA molecule to another Includes plasmids, transposons, genomic islands, phage DNA
Genomic islands
large DNA segments in genome that originated in other species
Characteristics encoded by genomic islands include
• Use of specific energy sources
• Acid tolerance
• Ability to cause disease
• Pathogenicity islands
CRISPR systems include
small segments of phage DNA that recognize the specific DNA if it invades the cell again
First invasion
complex of Cas proteins cuts DNA into short fragments
Subsequent invasion
transcription of CRISPR array generates crRNAs that direct DNA-cutting enzymes to invading DNA
Paul Ehrlich
Observed some dyes stain bacterial but not animal cells
Salvarsan
created by ehrlich
first antimicrobial medication
Red dye Prontosil
created by domagk
used to treat streptococcalinfections in animals
chemotherapeutic agents examples
Prontosil and Salvarsan
Antimicrobial medications, antimicrobial drugs, or antimicrobials
chemotherapeutic agents
Chemicals used to treat disease
Penicillium mold secretes
penicillin
antibiotic
naturally-producedantimicrobial
penicillin was the
first antibiotic
Most antibiotics come from microorganisms that normally live in
soil
Generating Antibiotic Incentives Now (GAIN) is U.S. law to
encourage companies to develop new antimicrobials against certain pathogens
Selective toxicity
causes greater harm to microbes than to human host
Toxicity is relative and expressed as
therapeutic index
therapeutic window
the range between the therapeutic dose and the toxic dose
Bacteriostatic
chemicals inhibit bacterial growth
Bactericidal
chemicals kill bacteria
Broad-spectrum antibiotics
affect a wide range and Disrupt microbiome that helps keep out other pathogens
Narrow-spectrum antibiotics
affect limited range and are Less disruptive to microbiome
Narrow-spectrum antibiotics require
identification and susceptibility of pathogen
antagonistic
Some medications interfere with others
synergistic
Some medications enhance one another
Patients with kidney or liver dysfunction excrete or metabolize medications more
slowly,
must adjust dosage to avoid toxic levels
Dysbiosis
imbalance in the microbiome
intrinsic (innate) resistance example
Mycoplasma lack cell wall, resistant to penicillin that interferes with peptidoglycan synthesis
how to develop acquired resistance
Spontaneous mutations
Horizontal gene transfer
Medication-inactivating enzymes
Bacteria produce enzymes that interfere with drug
Alteration in target molecule
Minor structural changes can prevent binding
Efflux pumps
remove compounds from cell
Gene transfer
Genes encoding resistance can spread to different strains, species, even genera
Resistance genes on R plasmids originate from
• Spontaneous mutations
• Microbes that naturally produce the antibiotic
Enterococci
part of normal intestinal microbiota
- Common cause of healthcare-associated infections
- Intrinsically less susceptible to many antimicrobials
vancomycin-resistant enterococci (VRE) is
transferable to other organisms
carbapenem-resistant Enterobacteriaceae (CRE)
Resistant to nearly all antibiotics
Multidrug-resistant tuberculosis (MDR-TB)
resist two favored first-line antibiotics: isoniazid and rifampin
Extensively drug-resistant tuberculosis (XDR-TB)
even greater concern, additionally resist three or more second-line anti- TB medications
Methicillin-resistant Staphylococcus aureus (MRSA)
Healthcare-associated (HA-MRSA) resistant to wide range of antibiotics, usually treated with vancomycin
Taxonomy
science that characterizes and names organisms to arrange them into hierarchical groups (taxa)
Identification
Process of characterizing in order to group
Classification
Arranging organisms into similar or related groups
Nomenclature
System of assigning names
Strategies Used to Identify Microorganisms
• Microscopic examination
• Culture characteristics
• Biochemical tests
• Nucleic acid analysis
• Patient symptoms (for pathogens)
Point-of-care testing (POCT)
testing done at or near the site of patient care
Phylogeny
considers evolutionary relatedness
Species in prokaryotes
group of closely related isolates or strains
Species
A group of closely related strains or individuals
Genus
A collection of similar species
Family
A collection of similar genera. In prokaryotic nomenclature, the name of the family ends in the suffix -aceae
Order
A collection of similar families. In prokaryotic nomenclature, the name of the order ends in the suffix -ales
Class
A collection of similar orders, names usually end in -ia
Phylum
(sometimes called a division) A collection of similar classes, names usually end in -ota
Kingdom
A collection of similar phyla or divisions
Domain
A collection of similar kingdoms. The domain reflects the characteristics of the cells that make up the organism
Current classification is three-domain system based on
nucleotide sequences in rRNA
Archaea Cytoplasmic membrane lipids
Hydrocarbons (not fatty acids) linked to glycerol by ether linkage
does Archaea have Membrane-bound nucleus
no
does archaea have introns
sometimes
archaea ribosomes
70s
Bacteria Cytoplasmic membrane lipids
Fatty acids linked to glycerol by ester linkage
does bacteria have introns
no
bacteria ribosomes
70s
Eukarya Cytoplasmic membrane lipids
Fatty acids linked to glycerol by ester linkage
do eukarya have introns
yes
eukarya ribosomes
80s
Bergey's Manual of Systematic Bacteriology
Describes all known prokaryotic species
• Classifies according to genetic relatedness (phylogeny)
International Code of Nomenclature of Prokaryotes
Provides rules for naming bacteria and archaea