pep27 and lytA in Vancomycin-Tolerant Pneumococci

Olivares, Alma; Trejo, Jose Olivares; Arellano‐Galindo, José; Zúñiga, Gerardo; Escalona, Gerardo; Vigueras, Juan Carlos; Marin, Paula A.; Xicohtencatl, Juan; Valencia, Pedro José Lozano; Velázquez-Guadarrama, Norma

doi:10.4014/jmb.1105.05045

Cited by 9 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even intense selective pressure by antibiotics has driven the emergence of downregulation of LytA activation, that is, tolerance, rather than elimination of the enzyme 44 . In fact, most penicillin-resistant isolates are tolerant but preserve lytA (refs 45 , 46 , 47 ). The majority of autolysin on a pneumococcal surface does not participate in lysis by antibiotics or induction of stationary phase lysis by quorum sensing as LytA is produced throughout growth, but activated only under certain circumstances 48 .…”

Section: Discussionmentioning

confidence: 99%

Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium

et al. 2016

View full text Add to dashboard Cite

Bacterial pathogens produce complex carbohydrate capsules to protect against bactericidal immune molecules. Paradoxically, the pneumococcal capsule sensitizes the bacterium to antimicrobial peptides found on epithelial surfaces. Here we show that upon interaction with antimicrobial peptides, encapsulated pneumococci survive by removing capsule from the cell surface within minutes in a process dependent on the suicidal amidase autolysin LytA. In contrast to classical bacterial autolysis, during capsule shedding, LytA promotes bacterial survival and is dispersed circumferentially around the cell. However, both autolysis and capsule shedding depend on the cell wall hydrolytic activity of LytA. Capsule shedding drastically increases invasion of epithelial cells and is the main pathway by which pneumococci reduce surface bound capsule during early acute lung infection of mice. The previously unrecognized role of LytA in removing capsule to combat antimicrobial peptides may explain why nearly all clinical isolates of pneumococci conserve this enzyme despite the lethal selective pressure of antibiotics.

show abstract

Section: Discussionmentioning

confidence: 99%

Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Moreover, it is unclear whether all filament forming enzymes are subject to enzymatic downregulation when assembled into cytoplasmic filaments. For example, it has long been known that polymerisation of acetyl Co-A carboxylase (ACC) upregulates enzymes activity, although it is unclear whether ACC forms equivalent macro-scale cytoplasmic structures ( Beaty and Lane, 1983a ; Beaty and Lane, 1983b ; Kleinschmidt et al, 1969 ; Olivares et al, 2011 ). Recently, it was demonstrated that glutamine synthase is regulated in a similar manner, indicating that downregulation of activity through polymerisation may be a widespread mechanism by which enzymes are regulated ( Petrovska et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism

et al. 2014

View full text Add to dashboard Cite

The essential metabolic enzyme CTP synthase (CTPsyn) can be compartmentalised to form an evolutionarily-conserved intracellular structure termed the cytoophidium. Recently, it has been demonstrated that the enzymatic activity of CTPsyn is attenuated by incorporation into cytoophidia in bacteria and yeast cells. Here we demonstrate that CTPsyn is regulated in a similar manner in Drosophila tissues in vivo. We show that cytoophidium formation occurs during nutrient deprivation in cultured cells, as well as in quiescent and starved neuroblasts of the Drosophila larval central nervous system. We also show that cytoophidia formation is reversible during neurogenesis, indicating that filament formation regulates pyrimidine synthesis in a normal developmental context. Furthermore, our global metabolic profiling demonstrates that CTPsyn overexpression does not significantly alter CTPsyn-related enzymatic activity, suggesting that cytoophidium formation facilitates metabolic stabilisation. In addition, we show that overexpression of CTPsyn only results in moderate increase of CTP pool in human stable cell lines. Together, our study provides experimental evidence, and a mathematical model, for the hypothesis that inactive CTPsyn is incorporated into cytoophidia.

show abstract

“…Tolerance was first described for ␤-lactam antibiotics, and the penicillin-tolerant phenotype was recognized in 1985 in eight clinical isolates of pneumococci (278). Tolerance to vancomycin has also been described in clinical isolates of S. pneumoniae (279)(280)(281)(282) and has been linked with treatment failure (279). While the mechanism of tolerance has not been fully elucidated, it has been suggested that tolerance is due to a faulty system of regulation of autolysins or changes in the composition of the cell wall (283).…”

Section: Antibiotic Tolerancementioning

confidence: 99%

“…While the mechanism of tolerance has not been fully elucidated, it has been suggested that tolerance is due to a faulty system of regulation of autolysins or changes in the composition of the cell wall (283). Several studies have suggested that the molecular mechanism of tolerance to penicillin and vancomycin involves a defect in the activation of LytA, a murein hydrolase that mediates an endogenous process of death leading to cellular lysis (281,284,285). Sung et al (285) also reported defective LytA autolysin and antimicrobial tolerance in clinical strains.…”

Section: Antibiotic Tolerancementioning

confidence: 99%

See 1 more Smart Citation

Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

et al. 2016

View full text Add to dashboard Cite

SUMMARYStreptococcus pneumoniaeinflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand.

show abstract

pep27 and lytA in Vancomycin-Tolerant Pneumococci

Cited by 9 publications

References 20 publications

Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium

Dynamic capsule restructuring by the main pneumococcal autolysin LytA in response to the epithelium

Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism

Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

Contact Info

Product

Resources

About