Novel mechanisms of macrolide resistance revealed by in vitro selection and genome analysis in Mycoplasma pneumoniae

Wang, Na; Xu, Xiaogang; Xiao, Li; Liu, Yang

doi:10.3389/fcimb.2023.1186017

Cited by 7 publications

(2 citation statements)

References 45 publications

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“…It has also been shown that ribosomal proteins can play a role in antibiotic resistance. Point mutations in the genes of some ribosomal proteins are responsible for acquiring resistance to macrolides and lincosamides ( Prats-van der Ham et al., 2018 ; Na Wang et al., 2023 ). It is possible that in the case of clinical isolates, the upregulation of ribosomal proteins plays an important role in their adaptation to host and requires further study of its role in adaptation.…”

Section: Resultsmentioning

confidence: 99%

Unraveling the adaptive strategies of Mycoplasma hominis through proteogenomic profiling of clinical isolates

Pobeguts,

Galaymina,

Sikamov

et al. 2024

Front. Cell. Infect. Microbiol.

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IntroductionMycoplasma hominis (M. hominis) belongs to the class Mollicutes, characterized by a very small genome size, reduction of metabolic pathways, including transcription factors, and the absence of a cell wall. Despite this, they adapt well not only to specific niches within the host organism but can also spread throughout the body, colonizing various organs and tissues. The adaptation mechanisms of M. hominis, as well as their regulatory pathways, are poorly understood. It is known that, when adapting to adverse conditions, Mycoplasmas can undergo phenotypic switches that may persist for several generations.MethodsTo investigate the adaptive properties of M. hominis related to survival in the host, we conducted a comparative phenotypic and proteogenomic analysis of eight clinical isolates of M. hominis obtained from patients with urogenital infections and the laboratory strain H-34.ResultsWe have shown that clinical isolates differ in phenotypic features from the laboratory strain, form biofilms more effectively and show resistance to ofloxacin. The comparative proteogenomic analysis revealed that, unlike the laboratory strain, the clinical isolates possess several features related to stress survival: they switch carbon metabolism, activating the energetically least advantageous pathway of nucleoside utilization, which allows slowing down cellular processes and transitioning to a starvation state; they reconfigure the repertoire of membrane proteins; they have integrative conjugative elements in their genomes, which are key mediators of horizontal gene transfer. The upregulation of the methylating subunit of the restriction-modification (RM) system type I and the additional components of RM systems found in clinical isolates suggest that DNA methylation may play a role in regulating the adaptation mechanisms of M. hominis in the host organism. It has been shown that based on the proteogenomic profile, namely the genome sequence, protein content, composition of the RM systems and additional subunits HsdM, HsdS and HsdR, composition and number of transposable elements, as well as the sequence of the main variable antigen Vaa, we can divide clinical isolates into two phenotypes: typical colonies (TC), which have a high growth rate, and atypical (aTC) mini-colonies, which have a slow growth rate and exhibit properties similar to persisters.DiscussionWe believe that the key mechanism of adaptation of M. hominis in the host is phenotypic restructuring, leading to a slowing down cellular processes and the formation of small atypical colonies. This is due to a switch in carbon metabolism and activation the pathway of nucleoside utilization. We hypothesize that DNA methylation may play a role in regulating this switch.

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Section: Resultsmentioning

confidence: 99%

Unraveling the adaptive strategies of Mycoplasma hominis through proteogenomic profiling of clinical isolates

Pobeguts,

Galaymina,

Sikamov

et al. 2024

Front. Cell. Infect. Microbiol.

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“…The mechanisms of macrolide resistance have been extensively studied. In addition to erm-mediated rRNA methylation and mef-mediated efflux [ 49 ], emphasis has been placed on mutations in 23S rRNA and ribosomal proteins [ 50 ]. These findings suggest that antibiotic use should be strictly regulated during estrus in animals.…”

Section: Discussionmentioning

confidence: 99%

Correlation between microbial characteristics and reproductive status of the yak uterus based on macrogenomic analysis

Wang,

Zeng

et al. 2024

BMC Vet Res

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Introduction This study aimed to investigate the microbial characteristics of yak uteri collected using intrauterine cotton swabs (CS) during different reproductive stages and the correlation of these microbial characteristics with reproductive status. Methods We used a macrogenomic approach to analyze the functional aspects of different microorganisms in samples collected during the pre-estrus, estrus, late estrus, and diestrus stages. Results The results revealed the presence of 1293 microbial genera and 3401 microbial species in the uteri of yaks at different reproductive stages. The dominant bacterial species varied across the different periods, with Micrococcus and Proteus being dominant during pre-estrus; Pseudomonas, Clostridium, Flavobacterium, Bacillus, and Staphylococcus during estrus; Acinetobacter, Bacillus and Proteus during late estrus; and Pseudomonas, Escherichia coli, and Proteus during diestrus. Discussion The primary functions of these bacteria are enriched in various metabolic pathways, including carbohydrate and amino acid metabolism, intracellular transport and secretion, post-translational protein modification, and drug resistance. These findings suggest that the microbial diversity in the uterus of yaks plays a crucial role in reproductive regulation and can help prevent reproductive tract-related diseases.

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Research of recombinant influenza A virus as a vector for Mycoplasma pneumoniae P1a and P30a

Yu,

Yongbo,

Shengjun

et al. 2024

Immunity Inflam & Disease

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BackgroundMycoplasma pneumoniae (MP) is a common respiratory pathogen affecting the longevity of the elderly and the health of children. However, the human vaccine against MP has not been successfully developed till now due to the poor immunogenicity and side effects of MP inactivated or attenuated vaccine. Therefore, it is necessary to develop a MP genetic engineering vaccine with influenza virus strain as vector.MethodsIn this study, the major antigen genes P1a of MP adhesion factor P1(3862‐4554 bases) and P30a of P30(49‐822 bases) were inserted into the nonstructural protein (NS) gene of Influenza A virus strain A/Puerto Rio/8/34(H1N1), PR8 for short, to construct the recombinant vectors NS‐P1a or NS‐P30a. The recombinant pHW2000 plasmids containing NS‐P1a or NS‐P30a were cotransfected with the rest 7 fragments of PR8 into HEK293T cells. After inoculating chicken embryos, the recombinant influenza viruses rFLU‐P1a and rFLU‐P30a were rescued. RT‐PCR and sequencing were used to identify the recombinant viruses. The hemagglutination titers of rFLU‐P1a and rFLU‐P30a were determined after five successive generations in chicken embryos so as to indicate the genetic stability of the recombinant viruses. The morphology of recombinant influenza viruses was observed under electron microscopy.ResultsP1a or P30a was designed to be inserted into the modified NS gene sequence separately and synthesized successfully. RT‐PCR identification of the recombinant viruses rFLU‐P1a and rFLU‐P30a showed that P1a (693 bp), P30a (774 bp), NS‐P1a (1992bp) and NS‐P30a (2073 bp) bands were found, and the sequencing results were correct. After five successive generations, each virus generation has a certain hemagglutination titer (from 1:32 to 1:64), and the band of P1a or P30a can be seen in the corresponding positions. The virus particles under the electron microscope appeared as spheres or long strips connected by several particles, revealing a complete viral membrane structure composed of virus lipid bilayer, hemagglutinin, neuraminidase, and matrix proteins.ConclusionThe recombinant viruses rFLU‐P1a and rFLU‐P30a which carried the advantaged immune regions of the P1 and P30 genes in MP were successfully constructed and identified. And the genetic stability of rFLU‐P1a or rFLU‐P30a was relatively high. The typical and complete morphology of influenza virus was observed under the electron microscope. Our research provided a foundation for the further development of MP vaccines for human.

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Novel mechanisms of macrolide resistance revealed by in vitro selection and genome analysis in Mycoplasma pneumoniae

Cited by 7 publications

References 45 publications

Unraveling the adaptive strategies of Mycoplasma hominis through proteogenomic profiling of clinical isolates

Unraveling the adaptive strategies of Mycoplasma hominis through proteogenomic profiling of clinical isolates

Correlation between microbial characteristics and reproductive status of the yak uterus based on macrogenomic analysis

Research of recombinant influenza A virus as a vector for Mycoplasma pneumoniae P1a and P30a

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