scholarly journals Mechanism of tetracycline resistance by ribosomal protection protein Tet(O)

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Wen Li ◽  
Gemma C. Atkinson ◽  
Nehal S. Thakor ◽  
Ülar Allas ◽  
Chuao-chao Lu ◽  
...  



2001 ◽  
Vol 7 (5) ◽  
pp. 1037-1045 ◽  
Author(s):  
Christian M.T. Spahn ◽  
Gregor Blaha ◽  
Rajendra K. Agrawal ◽  
Pawel Penczek ◽  
Robert A. Grassucci ◽  
...  


2007 ◽  
Vol 53 (12) ◽  
pp. 1307-1315 ◽  
Author(s):  
John J Macauley ◽  
Craig D. Adams ◽  
Melanie R. Mormile

Tetracycline resistance has been extensively studied and shown to be widespread. A number of previous studies have clearly demonstrated that a variety of tetracycline resistance genes are present in swine fecal material, treatment lagoons, and the environments surrounding concentrated animal feeding operations (CAFOs). The diversity of tetracycline resistance within a swine lagoon located at a CAFO that used only bacitricin methylene disalicylate as an antibiotic was evaluated by screening 85 tetracycline-resistant isolates for the presence of 18 different genes by performing PCR with primers that target tetracycline efflux genes of Gram-negative bacteria and ribosomal protection proteins. In addition, partial 16S rRNA sequences from each of these isolates were sequenced to determine the identity of these isolates. Of the 85 isolates examined, 17 may represent potential novel species based on BLAST results. Greater than 50% of the isolates (48 out of 85) were found to not contain targeted tet efflux genes. Though minimum inhibitory concentrations ranged widely (16 – >256 mg/L), these values did not give an indication of the tet genes present. Ten new genera were identified that contain at least one tet efflux gene. Five other genera possessed tet efflux genes that were not found in these organisms previously. Interestingly, none of the isolates possessed any of the selected ribosomal protection protein genes. Though tetracycline resistance was found in bacteria isolated from a swine CAFO lagoon, it appears that the limited antibiotic use at this CAFO might have impacted the presence and diversity of tetracycline resistance genes.



2013 ◽  
Vol 58 (3) ◽  
pp. 1279-1283 ◽  
Author(s):  
Michael P. Draper ◽  
S. Weir ◽  
A. Macone ◽  
J. Donatelli ◽  
C. A. Trieber ◽  
...  

ABSTRACTOmadacycline is a novel first-in-class aminomethylcycline with potent activity against important skin and pneumonia pathogens, including community-acquired methicillin-resistantStaphylococcus aureus(MRSA), β-hemolytic streptococci, penicillin-resistantStreptococcus pneumoniae,Haemophilus influenzae, andLegionella. In this work, the mechanism of action for omadacycline was further elucidated using a variety of models. Functional assays demonstrated that omadacycline is active against strains expressing the two main forms of tetracycline resistance (efflux and ribosomal protection). Macromolecular synthesis experiments confirmed that the primary effect of omadacycline is on bacterial protein synthesis, inhibiting protein synthesis with a potency greater than that of tetracycline. Biophysical studies with isolated ribosomes confirmed that the binding site for omadacycline is similar to that for tetracycline. In addition, unlike tetracycline, omadacycline is activein vitroin the presence of the ribosomal protection protein Tet(O).



Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 384
Author(s):  
Tessa de Block ◽  
Jolein Gyonne Elise Laumen ◽  
Christophe Van Dijck ◽  
Said Abdellati ◽  
Irith De Baetselier ◽  
...  

In this study, we characterized all oropharyngeal and anorectal isolates of Neisseria spp. in a cohort of men who have sex with men. This resulted in a panel of pathogenic Neisseria (N. gonorrhoeae [n = 5] and N. meningitidis [n = 5]) and nonpathogenic Neisseria (N. subflava [n = 11], N. mucosa [n = 3] and N. oralis [n = 2]). A high proportion of strains in this panel were resistant to azithromycin (18/26) and ceftriaxone (3/26). Whole genome sequencing (WGS) of these strains identified numerous mutations that are known to confer reduced susceptibility to azithromycin and ceftriaxone in N. gonorrhoeae. The presence or absence of these known mutations did not explain the high level resistance to azithromycin (>256 mg/L) in the nonpathogenic isolates (8/16). After screening for antimicrobial resistance (AMR) genes, we found a ribosomal protection protein, Msr(D), in these highly azithromycin resistant nonpathogenic strains. The complete integration site originated from Streptococcus pneumoniae and is associated with high level resistance to azithromycin in many other bacterial species. This novel AMR resistance mechanism to azithromycin in nonpathogenic Neisseria could be a public health concern if it were to be transmitted to pathogenic Neisseria. This study demonstrates the utility of WGS-based surveillance of nonpathogenic Neisseria.



1999 ◽  
Vol 43 (4) ◽  
pp. 738-744 ◽  
Author(s):  
P. J. Petersen ◽  
N. V. Jacobus ◽  
W. J. Weiss ◽  
P. E. Sum ◽  
R. T. Testa

ABSTRACT The 9-t-butylglycylamido derivative of minocycline (TBG-MINO) is a recently synthesized member of a novel group of antibiotics, the glycylcyclines. This new derivative, like the first glycylcyclines, theN,N-dimethylglycylamido derivative of minocycline and 6-demethyl-6-deoxytetracycline, possesses activity against bacterial isolates containing the two major determinants responsible for tetracycline resistance: ribosomal protection and active efflux. The in vitro activities of TBG-MINO and the comparative agents were evaluated against strains with characterized tetracycline resistance as well as a spectrum of recent clinical aerobic and anaerobic gram-positive and gram-negative bacteria. TBG-MINO, with an MIC range of 0.25 to 0.5 μg/ml, showed good activity against strains expressing tet(M) (ribosomal protection), tet(A), tet(B),tet(C), tet(D), and tet(K) (efflux resistance determinants). TBG-MINO exhibited similar activity against methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci, and vancomycin-resistant enterococci (MICs at which 90% of strains are inhibited, ≤0.5 μg/ml). TBG-MINO exhibited activity against a wide diversity of gram-negative aerobic and anaerobic bacteria, most of which were less susceptible to tetracycline and minocycline. The in vivo protective effects of TBG-MINO were examined against acute lethal infections in mice caused by Escherichia coli, S. aureus, andStreptococcus pneumoniae isolates. TBG-MINO, administered intravenously, demonstrated efficacy against infections caused byS. aureus including MRSA strains and strains containingtet(K) or tet(M) resistance determinants (median effective doses [ED50s], 0.79 to 2.3 mg/kg of body weight). TBG-MINO demonstrated efficacy against infections caused by tetracycline-sensitive E. coli strains as well asE. coli strains containing either tet(M) or the efflux determinant tet(A), tet(B), ortet(C) (ED50s, 1.5 to 3.5 mg/kg). Overall, TBG-MINO shows antibacterial activity against a wide spectrum of gram-positive and gram-negative aerobic and anaerobic bacteria including strains resistant to other chemotherapeutic agents. The in vivo protective effects, especially against infections caused by resistant bacteria, corresponded with the in vitro activity of TBG-MINO.





1995 ◽  
Vol 41 (11) ◽  
pp. 965-970 ◽  
Author(s):  
Diane E. Taylor ◽  
Lori J. Jerome ◽  
Jaswinder Grewal ◽  
Nicholas Chang

The tet(O) tetracycline resistance gene, originally cloned from Campylobacter jejuni, mediates resistance by ribosomal protection. Using partially purified Tet(O) protein of 68 000 Da whose identity was verified by ribosomal protection assays, amino terminal sequencing, and immunoblotting using an antibody raised against the deduced 15 amino acids at the carboxyl terminus of the Tet(O) protein, the Tet(O) protein was found to bind to [α-32P]GTP and [3H]GDP using a filter binding assay. [γ-32P]GTP hydrolysis by Tet(O) was also demonstrated and was found to be time dependent with more than 50% of the hydrolysis activity occurring within the first 5 min. The GTPase activity of Tet(O) appears to be ribosome dependent, suggesting that ribosomes act as an effector similar to other G proteins involved in signal transduction.Key words: ribosomes, tetracycline resistance, GTPase, protein synthesis.



2003 ◽  
Vol 47 (12) ◽  
pp. 3675-3681 ◽  
Author(s):  
Sean R. Connell ◽  
Dobryan M. Tracz ◽  
Knud H. Nierhaus ◽  
Diane E. Taylor


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