Micro 4

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