Rezistence
Aminoglycosides
- Acquired resistance by mutations in the ribosome target
- Presence of efflux mechanisms,
- Presence of most common enzymes which modify the antibiotic
- Resistance gene aacA-aphD found in the transposon Tn4001
- Confers resistance to gentamicin
- High-level resistant strains of different mycoplasma to several aminoglycosides
- By stepwise selection
- Resistance mechanism was not elucidated
- Used to cure cell cultures from mycoplasmal contamination, not human
- www.researchgate.net/publication/226918048_Antimycoplasmal_Agents
Chloramphenicol
- The cat gene encoding the chloramphenicol acetyltransferase
- Modifies and inactivates the antibiotic
- Selection marker in two non-human mollicutes and in M. pneumoniae
- www.researchgate.net/publication/226918048_Antimycoplasmal_Agents
Fluoroquinolones
- Quinolone resistance mechanisms
- Mutations in the four target genes, gyrA, gyrB, parC and parE
- Reduction in the level of quinolone accumulation inside the cells
- Active efflux
- Lack of penetration
- Target-related resistance for each gene, mutations cluster within a conserved region referred
- Quinolone resistance-determining region (QRDR)
- QRDRs were first described for GyrA and GyrB
- Homologous regions were identified later in the ParC and ParE enzymes
- High-level resistance associated with alterations in both DNA gyrase and topoisomerase IV.
- In the QRDRs of the gyrase gyrA gene and of the topoisomerase IV parC and parE genes
- BEBEAR AND BEBEAR gram-positive related organism
- Expression or over-expression of energy-dependent efflux pumps
- Actively remove antibacterials and other compounds
- Not yet been described in mycoplasmas
- My-bye in resistance to ciprofloxacin and ethidium bromide in the human mycoplasma M. hominis
MLS group - Acquired resistance to macrolides
- Reported during treatment with erythromycin
- Without affecting the clinical course of the illness
- Obtained in vitro by selection in the presence of erythromycin
- Presented an MLSB resistance phenotype
- Acquired resistance to macrolides, lincosamides and streptogramins B
- Erythromycin resistance of in vitro mutants of M. pneumoniae
- Associated with point mutations in the peptidyl transferase loop of domain V in the 23S rRNA,
- Leading to a target modification
- Two A→G transitions have been identified in positions 2058 and 2059
- Hot spots of macrolide resistance in other bacteria
- Lower affinity to erythromycin for ribosomes
- Patient with a chronic obstructive pulmonary disease
- Repetitively exposed to antibiotic treatments
- Showed a multi-resistance profile with additional resistance to fluoroquinolones
- Due to target alterations
- Josamycin resistence
- Associated with a mutation at position 2062 within domain V of the 23S rRNA
- Previously to be associated with macrolide resistance in other bacteria
- www.researchgate.net/publication/226918048_Antimycoplasmal_Agents
- Mycoplasma species are not affected by agents that interfere with
- The synthesis of folic acid
- Cell wall by beta-lactams and fosfomycin (Puglisi et al., 2000)
Resistance M. pneumoniae to
- ß-lactams
- Penicillins
- Cephalosporins
- Glycopeptides
- Sulfonamides
- Trimethoprim
- Polymixins
- Nalidixic acid
- Rifampin [5]
Resistance to tetracyclines
- MICs nad 8 ug/ml in M. hominis and Ureaplasma spp.
- Associated with the presence of the tetM determinant
- Conjugative transposon member of the Tn1545 family, named Tn916.
- Widely distributed among urogenital bacteria of human origin
- TetM transposon, Tn916,
- Present entirely in both M. hominis and Ureaplasma spp.
- Sole naturally acquired antibiotic resistance determinant in clinical strains of mycoplasmas.
- U. urealyticum
- 95 % homology at both DNA and peptidic sequence levels to tetM from the gram-positive genus, Streptococcus
- TetM determinant encodes the TetM protein
- Protects the ribosome from the action of tetracyclines
- Confers resistance to doxycycline and minocycline
- TetM protein
- Homology to elongation factors EF-Tu and EF-G
- Overlapping binding sites on ribosomes with EF-G
- Leads to a ribosomal conformational change preventing the tetracycline binding to ribosome
- Without altering protein synthesis
- Resistance varies geographically and according to prior antimicrobial exposure
- Frequency of resistant strains
- About 10% in patients attending STD clinics in United Kingdom
- About 5% in France
- Regulation of the expression of the tetM determinant
- TetM resistance gene
- Commonly used markers in genetic studies of mollicutes
- Transferred by conjugation or BEBEAR AND BEBEAR transformation
- High-level resistant strains of some mycoplasma species
- By stepwise selection in the presence of increasing concentrations of tetracyclines (71; Bébéar et al., unpublished data)
- www.researchgate.net/publication/226918048_Antimycoplasmal_Agents
