Effects of Subminimal Inhibitory Concentrations of Antibiotics in Experimental Infections

Zak, O.; Kradolfer, F

doi:10.1093/clinids/1.5.862

Cited by 75 publications

(38 citation statements)

References 27 publications

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“…Proteins of the Fts family are required for the division of enteric bacteria but not cellular growth or replication of DNA (1,3,7,10,46,62). The amounts of FtsZ and PBP3 (FtsI) were quantified via immunoblot to address whether the levels of individual Fts proteins differed in osmotically stressed and unstressed cells.…”

Section: Resultsmentioning

confidence: 99%

“…Likewise, hydrostatic pressure, the SOS response via SulA, and antimicrobials, such as berberine and cinnamaldehyde, induce filamentation of E. coli by preventing the polymerization of FtsZ (5,12,13,24,30,39,55). ␤-Lactam antibiotics that bind penicillin-binding protein 3 (PBP3, also known as FtsI) inhibit its enzymatic activity and septum formation but not cellular growth (46,62).…”

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confidence: 99%

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Characterization of Osmotically Induced Filaments of Salmonella enterica

Pratt

Chen

Czuprynski

et al. 2012

Appl Environ Microbiol

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ABSTRACTSalmonella entericaforms aseptate filaments with multiple nucleoids when cultured in hyperosmotic conditions. These osmotic-induced filaments are viable and form single colonies on agar plates even though they contain multiple genomes and have the potential to divide into multiple daughter cells. Introducing filaments that are formed during osmotic stress into culture conditions without additional humectants results in the formation of septa and their division into individual cells, which could present challenges to retrospective analyses of infectious dose and risk assessments. We sought to characterize the underlying mechanisms of osmotic-induced filament formation. The concentration of proteins and chromosomal DNA in filaments and control cells was similar when standardized by biomass. Furthermore, penicillin-binding proteins in the membrane of salmonellae were activein vitro. The activity of penicillin-binding protein 2 was greater in filaments than in control cells, suggesting that it may have a role in osmotic-induced filament formation. Filaments contained more ATP than did control cells in standardized cell suspensions, though the levels of two F0F1-ATP synthase subunits were reduced. Furthermore, filaments could septate and divide within 8 h in 0.2× Luria-Bertani broth at 23°C, while nonfilamentous control cells did not replicate. Based upon the ability of filaments to septate and divide in this diluted broth, a method was developed to enumerate by plate count the number of individual, viable cells within a population of filaments. This method could aid in retrospective analyses of infectious dose of filamented salmonellae.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Characterization of Osmotically Induced Filaments of Salmonella enterica

Pratt

Chen

Czuprynski

et al. 2012

Appl Environ Microbiol

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“…Bacteria respond to stresses such as oxidative stress (8), nutrient stress (36), DNA damage (22), and some antibiotics (21,37) by arresting DNA replication and/or cell division. Filamentous uropathogenic Escherichia coli have been observed during infection of bladder epithelial cells (38).…”

Section: Discussionmentioning

confidence: 99%

Macrophages Inhibit Salmonella Typhimurium Replication through MEK/ERK Kinase and Phagocyte NADPH Oxidase Activities

Rosenberger¹,

Finlay

2002

Journal of Biological Chemistry

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Host responses during the later stages of Salmonellamacrophage interactions are critical to controlling infection but have not been well characterized. After 24 h of infection, nearly half of interferon-␥-primed murine RAW 264.7 macrophage-like cells infected by Salmonella enterica serovar Typhimurium contained filamentous bacteria. Bacterial filamentation indicates a defect in completing replication and has been previously observed in bacteria responding to a variety of stresses. To understand whether macrophage gene expression was responsible for this effect on Salmonella Typhimurium replication, we used gene arrays to profile interferon-␥-primed RAW 264.7 cell gene expression following infection. We observed an increase in MEK1 kinase mRNA at 8 h, an increase in MEK protein at 24 h, and measured phosphorylation of MEK's downstream target kinase, ERK1/2, throughout the 24-h infection period. Treatment of cells with MEK kinase inhibitors significantly reduced numbers of filamentous bacteria observed within macrophages after 24 h and increased the number of intracellular colony-forming units. Phagocyte NADPH oxidase inhibitors and antioxidants also significantly reduced bacterial filamentation. Either MEK kinase or phagocyte oxidase inhibitors could be added 4 -8 h after infection and still significantly decrease bacterial filamentation. Oxidase activity appears to mediate bacterial filamentation in parallel to MEK kinase signaling, while inducible nitric-oxide synthase inhibitors had no significant effect on bacterial morphology. In summary, Salmonella Typhimurium infection of interferon-␥-primed macrophages triggers a MEK kinase cascade at later infection times, and both MEK kinase and phagocyte NADPH oxidase activity impair bacterial replication. These two signaling pathways mediate a host bacteriostatic pathway and may play an important role in innate host defense against intracellular pathogens.

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“…1 and Fig. 2a (22,36). In a recent study we reported that cephalosporin antibiotics at a concentration as low as 1/10 of the MIC caused morphological alterations, reduced the production of enterochelin and capsular materials, and potentiated the agglutination by serum prepared against a nonencapsulated strain of K. pneumoniae (20).…”

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confidence: 85%

Protein antigens of encapsulated Klebsiella pneumoniae surface exposed after growth in the presence of subinhibitory concentrations of cephalosporins

Kadurugamuwa¹,

Anwar²,

Brown³

et al. 1985

Antimicrob Agents Chemother

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It recently has been reported by us that cephalosporins, at a concentration below that influencing growth rate, reduced the prQduction of enterochelin and capsule formation of iron-depleted Klejsiella pneumoniae. We now report on the antigenicity of the outer membrane components and surface-exposed protein antigens of iron-depleted cells grown in the presencp or absence of cephalosporins. All major outer membrane proteins, including iron-regulated membrane proteins, were immunogenic. Encapsulated K. pneumoniae grown in antibiotic-free media had three protein antigens (60, 35.5, and 32.5 kilodaltons) exposed on the surface that were accessible to antibodies. Growth of the same cultures in the presence of subinhibitory concentrations of cephalosporins resulted in the exposure of a greater number of protein antigenic determinants, including iron-regulated membrane proteins, which become readily accessible to antibodies. It was also found that immunoblotting was generally more sensitive than conventional staining of the acrylamide gel with Coomnassie blue in the detection of proteins.

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Effects of Subminimal Inhibitory Concentrations of Antibiotics in Experimental Infections

Cited by 75 publications

References 27 publications

Characterization of Osmotically Induced Filaments of Salmonella enterica

Characterization of Osmotically Induced Filaments of Salmonella enterica

Macrophages Inhibit Salmonella Typhimurium Replication through MEK/ERK Kinase and Phagocyte NADPH Oxidase Activities

Protein antigens of encapsulated Klebsiella pneumoniae surface exposed after growth in the presence of subinhibitory concentrations of cephalosporins

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