INF1 - F. RESISTANCE MECHANISMS-COVERED Flashcards
what is antibiotic resistance
when bacteria survive exposure to 1 or more antibiotics
what is intrinsic resistance
natural resistance of a bacterial species to antibiotics
1. lack of target
2. lack of permeability
what is acquired resistance
develops in previously sensitive cells following mutations or transfer of genetic information (plasmids) between cells
- conjugation: sexual contact between bacteria
- transformation: DNA from environment through bacteria which have been damaged
- transduction: DNA transferred from 1 bacterium to another by a bacteriophage (virus)
4 mechanisms which cause resistance
- reduced cellular uptake
- inactivation of antibiotic
- alteration/mutation of target/increased expression of target
- increased efflux of antibiotic
what causes reduced uptake
has a negative charge, can reduce uptake due to LPS, mycolic acid of gram -ve outer membrane
what causes inactivation
beta-lactamases made by bacteria in response to beta-lactam antibiotics
what causes altered target
- mutation (PBPs)
- alternative pathway so bacteria can still achieve its metabolic process
- increased expression of target
what causes efflux
multiple types of pumps
varied expression/activity
what causes resistance to beta-lactam antibiotics
- beta-lactamases (mainly in gram-ve bacteria)
- few beta-lactam resistant bacteria don’t produce beta-lactamases
- target modification (PBP mutation)
- reduced uptake
how are beta-lactamases produced
genetic transfer and subsequent expression of the enzyme
>300 types
what drugs were developed due to lactamase-producing strains
- 3rd gen cephlasporins
- lactamase inhibitors: clavulanic acid with amoxicillin - co-amoxiclav
how does clavulanic work as a decoy
- possesses a beta-lactam ring but not active and hence a decoy target for lactamase enzyme which binds to molecule and inhibits enzymes
- only effective against serine beta-lactamases
what are extended spectrum beta-lactamases
- mutant lactamases that inactivate most/all beta-lactam antibiotics (mainly gram-ve)
- mutations are easily transferred to other bacteria via conjugation
- extrachromosomal DNA on plasmids - genes that encode molecules that are important in pathogenicity and also resistant to antibiotics ie - production of beta-lactamases
- produced by klebsiella app. and Escherichia coli strains
- many ESBLs not inhibited by clavulanic acid
- example of counter adaptation by bacteria
how does resistance to PBPs occur
- genetic transfer and subsequent expression of genes
- that lead to expression of mutated PBPs (MRSA, C. diff) and antibiotic no longer binds
how does a change of outer membrane permeability cause resistance to beta-lactams
- porins in OM of gram -ve bacteria
- decreased porin expression or mutations
- LPS confers a -ve charge, impedes entry of beta-lactams due to charge effects and hydrophobicity
what bacteria most commonly causes CAP
- Streptococcus pneumonia
- Gram+ve cocci (pairs)
- In nasopharyngeal region
- Infection if enter eyes/lungs or following viral infection
- Part of microbiome but causes infection when has opportunity
pathogenicity factors of Streptococcus pneumoniae
- polysaccharide capsule: protects from phagocytosis
- phosphorylcholine in cell wall: helps binding to mammalian cells which engulf the and aid transit into blood (meningitis and sepsis)
- adhesin: binding to epithelial cells in airway
- IgA protease: destroys body’s natural immunoglobulins
- Pneumolysin: binds to cholesterol in mammalian epithelial cell membrane, producing pores and cell lysis - streptococcal meningitis
how does resistance to beta-lactams of Streptococcus pneumonia occur
- mutations in PBPs
- resistance for macrolides (altered target in ribosome and efflux) and fluororquinolones (altered topoisomerase)
where is haemophilus influenzae found
- nasal pharyngeal
- part of microbiome
- gram -ve coccobacillus
- at least 6 strains (type B/Hib most prominent - vaccine for infant Hip against capsular polysaccharide)
- spread in respiratory droplets
pathogenicity factors of haemophilus influenzae
- polysaccharide capsule: binds to penetration of epithelia and resisting phagocytosis
what infections does haemophilus influenzae cause
pneumonia
conjunctivitis
dental abscesses
middle-ear infections
meningitis
why is haemophilus influenzae resistant to many antibiotics
altered PBP
beta-lactamases
efflux
where does chlamydia and gonorrhoea affect
eyes
mouth/throat
uterus
genital/urinary tract
rectum/anus
what causes chlamydia and gonorrhoea
unprotected sex (oral, vaginal, anal)
touching/transfer with fingers/genitals/sex toys
can be passed from untreated mothers to new born babies
*those with gonorhoea are often also infected with chlamydia
