SOS Response Induction by ß-Lactams and Bacterial Defense Against Antibiotic Lethality

Miller, Christine; Thomsen, Line Elnif; Gaggero, Carina; Mosseri, Ronen; Ingmer, Hanne; Cohen, Stanley N.

doi:10.1126/science.1101630

Cited by 489 publications

(384 citation statements)

References 21 publications

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“…We note in closing that the recognition that cells must be in a state of division for rapid lysis by FtsI-selective ␤-lactams may have important clinical implications since FtsI selective ␤-lactams are widely used. Whether actively induced or a by-product of stress brought on by the host immune response, filamentation is a key survival strategy for a variety of bacterial pathogens, including E. coli, Mycobacterium tuberculosis, Salmonella, and Legionella (31,32). While FtsN does not appear in all bacterial species, we presume that all species use some sensing mechanism to ensure that cell wall synthesis and degradation are coordinated.…”

Section: Discussionmentioning

confidence: 91%

Rapid β-lactam-induced lysis requires successful assembly of the cell division machinery

Chung

Yao

Goehring³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

107

115

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␤-lactam antibiotics inhibit penicillin binding proteins (PBPs) involved in peptidoglycan synthesis. Although inhibition of peptidoglycan biosynthesis is generally thought to induce cell lysis, the pattern and mechanism of cell lysis can vary substantially. ␤-lactams that inhibit FtsI, the only division specific PBP, block cell division and result in growth as filaments. These filaments ultimately lyse through a poorly understood mechanism. Here we find that one such ␤-lactam, cephalexin, can, under certain conditions, lead instead to rapid lysis at nascent division sites through a process that requires the complete and ordered assembly of the divisome, the essential machinery involved in cell division. We propose that this assembly process (in which the localization of cell wall hydrolases depends on properly targeted FtsN, which in turn depends on the presence of FtsI) ensures that the biosynthetic machinery to form new septa is in place before the machinery to degrade septated daughter cells is enabled. ␤-lactams that target FtsI subvert this mechanism by inhibiting FtsI without perturbing the normal assembly of the cell division machinery and the consequent activation of cell wall hydrolases. One seemingly paradoxical implication of our results is that ␤-lactam therapy may be improved by promoting active cell division.amidase ͉ cell wall hydrolase ͉ ftsN ͉ penicillin-binding proteins ͉ peptidoglycan

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Section: Discussionmentioning

confidence: 91%

Rapid β-lactam-induced lysis requires successful assembly of the cell division machinery

Chung

Yao

Goehring³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

107

115

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“…Ampicillin induces filamentation 18,19 (Fig. 3E), a property shared by many other stresses (including the antibiotic groups cephalosporins and quinolones 20 and UV Figure 2.…”

Section: Resultsmentioning

confidence: 99%

General calibration of microbial growth in microplate readers

Stevenson

McVey

Clark

et al. 2016

Preprint

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Optical density (OD) measurements of microbial growth are one of the most common techniques used in microbiology, with applications ranging from studies of antibiotic efficacy to investigations of growth under different nutritional or stress environments, to characterization of different mutant strains, including those harbouring synthetic circuits. OD measurements are performed under the assumption that the OD value obtained is proportional to the cell number, i.e. the concentration of the sample. However, the assumption holds true in a limited range of conditions, and calibration techniques that determine that range are currently missing. Here we present a set of calibration procedures and considerations that are necessary to successfully estimate the cell concentration from OD measurements.Bacteria and yeast are widely studied microorganisms of great economic, medical and societal interest. Much of our understanding of bacterial and yeast life cycles stems from monitoring their proliferation in time and the most routine way of doing so is using optical density (OD) measurements. The applications of such measurements range from routine checks during different cloning techniques 1 ; through studying cellular physiology and metabolism 2,3 ; to determining the growth rate for antibiotic dosage 4,5 ; and monitoring of biomass accumulation during bio-industrial fermentation 6 . Here we introduce a set of calibration techniques that take into account the relevant parameters affecting OD measurements, including at high culture densities, in a range of conditions commonly used by researchers.OD measurements have become synonymous with measurements of bacterial number (N) or concentration (C), in accordance with the Beer-Lambert law. However, OD measurements are turbidity measurements 7,8 , thus the Beer-Lambert law can be applied, with some considerations, only for microbial cultures of low densities. OD measurements in plate readers, increasingly used for high-throughput estimates of microbial growth, operate predominantly at higher culture densities where OD is expected to have a parabolic dependency on N 8 . Additionally, the proportionality constants (either in low or high density regimes) strongly depend on several parameters, for example cell size, which need to be included in robust calibration techniques. Yet, these techniques, essential when using OD measurements for quantitative studies of microbial growth, including growth rates, lag times and cell yields, have thus far not been established.The Beer-Lambert law (Supplementary Note 1) assumes that light is only absorbed to derive OD ~ C, which is true if the light received by the detector of a typical spectrophotometer is the light that did not interact with the sample in any way 7,9 . In general, when microbial cells are well dispersed in the solution (for the cases where N is small, i.e. single scattering regime) and the geometry of the spectrophotometer is suitable, the Beer-Lambert law is a good approximation for turbidity measurements, and N (or C) is ~...

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“…La présence naturelle dans l'environnement de faibles quantités d'antibiotiques sécrétées par des champignons et certaines bacté-ries (par exemple les actinomycètes) constitue une forte pression sélective pour l'émergence de stratégies de résis-tance. La filamentation chez les bacté-ries en présence de certains antibiotiques en est une [10] et cette stratégie s'avère avantageuse pour l'évolution. Les phages, quant à eux, profitent de la physiologie altérée de ces bactéries « stressées » pour amplifier le nombre de phages produits par cycle d'infection par rapport aux situations plus saines.…”

Section: Intérêt De L'interaction Phages-antibiotiques Pour L'équilibunclassified

La « synergie phages-antibiotiques »

et al. 2008

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SOS Response Induction by ß-Lactams and Bacterial Defense Against Antibiotic Lethality

Cited by 489 publications

References 21 publications

Rapid β-lactam-induced lysis requires successful assembly of the cell division machinery

Rapid β-lactam-induced lysis requires successful assembly of the cell division machinery

General calibration of microbial growth in microplate readers

La « synergie phages-antibiotiques »

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