ArticleApplied and environmental microbiology2015
Novel functions of (p)ppGpp and Cyclic di-GMP in mycobacterial physiology revealed by phenotype microarray analysis of wild-type and isogenic strains of Mycobacterium smegmatis.
Article in Applied and environmental microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 78 citations in OpenAlex.
- De novo or Salvage? Nucleotide Availability as a Driver of Bacterial Adaptation and Virulence.MicrobiologyOpen · 2026Review
- The ppGpp-HpaR1-gum regulatory pathway modulates exopolysaccharides production in Xanthomonas campestris pv. campestris.NPJ biofilms and microbiomes · 2026Article
- Impairment of two non-essential LytR-cpsA-psr (Lcp) cell wall ligases decelerate cell wall assembly in Mycolicibacterium smegmatis.BMC microbiology · 2026Article
- Exploring the evolutionary divergence of cyclic di-nucleotide signaling in diverse mycobacterial species.Archives of microbiology · 2026Article
- Expression ofFrontiers in cellular and infection microbiology · 2025Article
- Diversity of Transcriptional Regulatory Adaptation in E. coli.Molecular biology and evolution · 2024Article
- Development and Regulation of the Extreme Biofilm Formation ofInternational journal of molecular sciences · 2023Article
- A Loss of Function in LprG-Rv1410c Homologues Attenuates Growth during Biofilm Formation inPathogens (Basel, Switzerland) · 2023Article
- Population heterogeneity inMicrobiology (Reading, England) · 2023Article
- Tale of Twin Bifunctional Second Messenger (p)ppGpp Synthetases and Their Function in Mycobacteria.ACS omega · 2023Review
- "Sharing the matrix" - a cooperative strategy for survival in Salmonella enterica serovar Typhimurium.BMC microbiology · 2023Article
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- Elucidating the role of c-di-AMP inHeliyon · 2023Article
- Aza-Michael promoted glycoconjugation of PETIM dendrimers and selectivity in mycobacterial growth inhibitions.RSC advances · 2023Article
- Expression of a novel mycobacterial phosphodiesterase successfully lowers cAMP levels resulting in reduced tolerance to cell wall-targeting antimicrobials.The Journal of biological chemistry · 2022Article
- InJournal of bacteriology · 2022Article
- Intercellular communication and social behaviors in mycobacteria.Frontiers in microbiology · 2022Review
- Article
- Stringent Response in Mycobacteria: From Biology to Therapeutic Potential.Pathogens (Basel, Switzerland) · 2021Review
- Understanding Metabolic Remodeling inFrontiers in microbiology · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bacterial second messengers (p)ppGpp and bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulate important functions, such as transcription, virulence, biofilm formation, and quorum sensing. In mycobacteria, they regulate long-term survival during starvation, pathogenicity, and dormancy. Recently, a Pseudomonas aeruginosa strain lacking (p)ppGpp was shown to be sensitive to multiple classes of antibiotics and defective in biofilm formation. We were interested to find out whether Mycobacterium smegmatis strains lacking the gene for either (p)ppGpp synthesis (ΔrelMsm) or c-di-GMP synthesis (ΔdcpA) would display similar phenotypes. We used phenotype microarray technology to compare the growth of the wild-type and the knockout strains in the presence of several antibiotics. Surprisingly, the ΔrelMsm and ΔdcpA strains showed enhanced survival in the presence of many antibiotics, but they were defective in biofilm formation. These strains also displayed altered surface properties, like impaired sliding motility, rough colony morphology, and increased aggregation in liquid cultures. Biofilm formation and surface properties are associated with the presence of glycopeptidolipids (GPLs) in the cell walls of M. smegmatis. Thin-layer chromatography analysis of various cell wall fractions revealed that the levels of GPLs and polar lipids were reduced in the knockout strains. As a result, the cell walls of the knockout strains were significantly more hydrophobic than those of the wild type and the complemented strains. We hypothesize that reduced levels of GPLs and polar lipids may contribute to the antibiotic resistance shown by the knockout strains. Altogether, our data suggest that (p)ppGpp and c-di-GMP may be involved in the metabolism of glycopeptidolipids and polar lipids in M. smegmatis.
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