A Phase 2, Multicenter, Randomized, Open-Label, Comparative Study to Evaluate the Safety and Efficacy of RX-1741 Versus Linezolid in the Outpatient Treatment of Adult Patients With Uncomplicated Skin and Skin Structure Infection

The purpose of this study is to assess the efficacy, safety and tolerability of RX-1741, an oxazolidinone, versus linezolid, another oxazolidinone, in the treatment of uncomplicated skin and skin structure infections

Start Date01 Dec 2007

Sponsor / Collaborator

Melinta Therapeutics, Inc.

NCT00640926

/ CompletedPhase 2

A Phase 2, Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of RX-1741 in the Treatment of Adult Patients With Mild to Moderate Severity of Community-Acquired Pneumonia (CAP)

The purpose of this study is to determine whether RX-1741, an oxazolidinone antibiotic, is safe and effective in the treatment of mild to moderate community acquired pneumonia (CAP).

Start Date01 Oct 2007

Sponsor / Collaborator

Melinta Therapeutics, Inc.

100 Clinical Results associated with 23S rRNA

100 Translational Medicine associated with 23S rRNA

0 Patents (Medical) associated with 23S rRNA

2,264

Literatures (Medical) associated with 23S rRNA

25 Apr 2025·Journal of Medical Microbiology

Mycoplasma genitalium molecular typing in men with non-gonococcal urethritis discriminates between phylogenetic clusters based on sexual preference and antibiotic resistance

Article

Author: Adriaens, Nikki ; Westerhuis, Brenda M. ; Bruisten, Sylvia M. ; Doelman, Tessa A. ; Vergunst, Clarissa E. ; van Dam, Alje P. ; Bouwman, Fenna M.

Introduction.Mycoplasma genitalium is a sexually transmitted bacterium associated with non-gonococcal urethritis (NGU) in men. The rising macrolide and fluoroquinolone resistance in M. genitalium has become a public health concern, requiring close surveillance.Gap statement.MgpB/MG309 typing is commonly used to study genotype distribution and resistance patterns of M. genitalium in men who have sex with men (MSM); however, data for men who have sex with women (MSW) are limited.Aim. The aim of this study was to explore the epidemiology of M. genitalium based on mgpB/MG309 molecular typing in isolates from men diagnosed with NGU, comparing MSM and MSW. Additionally, antibiotic resistance was evaluated to assess associations between the mgpB/MG309 genotypes, antimicrobial resistance profiles, and epidemiological determinants.Methodology. A subset of previously collected M. genitalium isolates from men diagnosed with NGU in Amsterdam, the Netherlands, between May 2018 and November 2019 was analysed. Molecular typing was performed by sequencing relevant regions of the mgpB and MG309 loci. Macrolide resistance was assessed by detecting mutations in the 23S rRNA gene via quantitative polymerase chain reaction, while fluoroquinolone resistance was determined through sequencing parC and gyrA.Results. A total of 62 M. genitalium samples were analysed from 33 MSM and 29 MSW. The overall macrolide and fluoroquinolone resistance was 75.8% and 24.2 %, respectively. At the mgpB locus, 24 sequence types (STs) were identified, with ST4 most prevalent in MSM and ST2 in MSW. The MG309 locus revealed 12 distinct short tandem repeat numbers, with repeat 10 being most common in both groups. Phylogenetic analysis based on mgpB sequences revealed two clusters: cluster A included significantly more MSW, whereas cluster B predominantly comprised MSM (P<0.001). Macrolide and fluoroquinolone resistance was significantly higher in cluster B compared with cluster A (P<0.01 and P<0.05, respectively).Conclusion. Molecular typing of M. genitalium revealed two clusters that differed by sexual preference and antibiotic resistance, highlighting the importance of surveillance of resistance across genotypes. The findings suggest multiclonal spread of resistance through independent mutations. Future studies using next-generation sequencing are needed to further explore the links between sexual transmission and genetic diversity in M. genitalium.

02 Apr 2025·Journal of Antimicrobial Chemotherapy

Surveying genetic markers of antibiotic resistance and genomic background in Chlamydia trachomatis: insights from a multiplex NGS-based approach in clinical strains from Portugal

Article

Author: Cordeiro, Dora ; Aliyeva, Elzara ; Borrego, Maria José ; Vieira, Luís ; Correia, Cristina ; Portugal, Clara ; Carreira, Teresa ; Duarte, Sílvia ; Costa Da Silva, Jorge ; Gomes, João Paulo ; Matos, Susana ; Côrte-Real, Rita ; Carpinteiro, Dina ; João, Inês ; Lodhia, Zohra ; Monge, Isabel ; Borges, Vítor ; Schäfer, Sandra ; Dias, Ana Paula ; Gonçalves, Elsa

AbstractObjectivesTo survey genetic markers of potential antimicrobial resistance (AMR) to macrolides and fluoroquinolones among Chlamydia trachomatis–positive samples from the collection of the Portuguese National Reference Laboratory for Sexually Transmitted Infections (STIs), and explore a multiplex PCR approach coupled with NGS to provide complementary information regarding a strain’s genomic backbone.MethodsA total of 502 C. trachomatis–positive samples, mostly anorectal exudates, were subjected to PCR and sequencing of five targets, including loci potentially driving AMR (23S rRNA, gyrA and parC) and loci potentially informative about a strain’s genomic backbone with emphasis on differentiation of lymphogranuloma venereum (LGV)/non-LGV and L2/L2b (a 9 bp insertion in pmpH, a 74 bp insertion upstream from CT105 and the polymorphic CT442).ResultsNo samples evidenced 23S rRNA mutations recognizably linked to macrolide resistance. Three samples harboured the Ser83Ile mutation in GyrA putatively driving fluoroquinolone resistance: two recombinant L2-L2b/D-Da (0.4%) and one L2 (0.2%). The screened regions in pmpH, upstream CT105 and CT442 were fully concordant with LGV/non-LGV differentiation. As expected, the pmpH L2b-specific genetic trait locus was detected in all L2b and recombinant L2-L2b/D-Da ompA genotypes, but also in 96.0% of L2 specimens, which also likely possess an L2b genomic backbone. The insertion upstream from CT105 exhibited full LGV specificity, constituting a promising target for the development of rapid LGV diagnostic assays.ConclusionsThis study contributes to enhancing the knowledge of C. trachomatis molecular epidemiology, suggesting that the known genetic determinants of AMR are not disseminated in clinical C. trachomatis strains, and presents an exploratory approach that can be suitable for LGV/non-LGV and L2/L2b genomic background differentiation.

01 Apr 2025·RNA

Role of the sarcin-ricin loop of 23S rRNA in biogenesis of the 50S ribosomal subunit

Article

Author: Moon, Kyung-Mee ; Aval, Sepideh Fakhretaha ; Ortega, Joaquin ; Seffouh, Amal ; Fredrick, Kurt ; Foster, Leonard J

The sarcin-ricin loop (SRL) is one of the most conserved segments of ribosomal RNA (rRNA). Translational GTPases (trGTPases), such as EF-G, EF-Tu, and IF2, form contacts with the SRL that are critical for GTP hydrolysis and factor function. Previous studies showed that expression of 23S rRNA lacking the SRL confers a dominant lethal phenotype inEscherichia coli. Isolated ΔSRL particles were found to be not only inactive in protein synthesis but also incompletely assembled. In particular, block 4 of the subunit, which includes the peptidyl transferase center, remained unfolded. Here, we explore the basis of this assembly defect. We find that 23S rRNA extracted from ΔSRL subunits can be efficiently reconstituted into 50S subunits, and these reconstituted ΔSRL particles exhibit full peptidyl transferase activity. We also further characterize ΔSRL particles purified from cells, using cryo-EM and proteomic methods. These particles lack density for rRNA and r-proteins of block 4, consistent with earlier chemical probing data. Incubation of these particles with excess total r-protein of the large subunit (TP50) fails to restore substantial peptidyl transferase activity. Interestingly, proteomic analysis of control and mutant particles shows an overrepresentation of multiple assembly factors in the ΔSRL case. We propose that one or more GTPases normally act to release assembly factors, and this activity is blocked in the absence of the SRL.

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