Identification of Agents Targeting Ftsz Assembly

Panda, Dulal; Bhattacharya, Dipanwita; Gao, Quanqing; Oza, Pratik M.; Lin, H-Y Jennifer; Hawkins, Bryson A.; Hibbs, David E.; Groundwater, Paul W.

doi:10.4155/fmc-2016-0041

Cited by 29 publications

(29 citation statements)

References 128 publications

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“…Other genes essential in both KIM1001 and CO92 which encode gene products unique to bacteria, such as the FtsZ cell division protein, the twin arginine transport (Tat) system and the SurA chaperone, encode potential drug targets. For example, currently there is significant interest in developing inhibitors of FtsZ [59]. Our study also identified novel targets for antimicrobial drugs including the hypothetical proteins YPO3498, YPO3579, YPO3586 and YPO3665/6/7 which encode the rod shape-determining proteins MreB, MreC and MreD respectively.…”

Section: Resultsmentioning

confidence: 82%

An integrated computational-experimental approach reveals Yersinia pestis genes essential across a narrow or a broad range of environmental conditions

et al. 2017

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BackgroundThe World Health Organization has categorized plague as a re-emerging disease and the potential for Yersinia pestis to also be used as a bioweapon makes the identification of new drug targets against this pathogen a priority. Environmental temperature is a key signal which regulates virulence of the bacterium. The bacterium normally grows outside the human host at 28 °C. Therefore, understanding the mechanisms that the bacterium used to adapt to a mammalian host at 37 °C is central to the development of vaccines or drugs for the prevention or treatment of human disease.ResultsUsing a library of over 1 million Y. pestis CO92 random mutants and transposon-directed insertion site sequencing, we identified 530 essential genes when the bacteria were cultured at 28 °C. When the library of mutants was subsequently cultured at 37 °C we identified 19 genes that were essential at 37 °C but not at 28 °C, including genes which encode proteins that play a role in enabling functioning of the type III secretion and in DNA replication and maintenance. Using genome-scale metabolic network reconstruction we showed that growth conditions profoundly influence the physiology of the bacterium, and by combining computational and experimental approaches we were able to identify 54 genes that are essential under a broad range of conditions.ConclusionsUsing an integrated computational-experimental approach we identify genes which are required for growth at 37 °C and under a broad range of environments may be the best targets for the development of new interventions to prevent or treat plague in humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-1073-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 82%

An integrated computational-experimental approach reveals Yersinia pestis genes essential across a narrow or a broad range of environmental conditions

et al. 2017

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“…By using docking approaches, the authors suggest that their compounds might bind to the cell division protein FtsZ. Although these predictions are far away to be confirmed, anti‐FtsZ antimicrobials should constitute a novel group of antibiotics with clear clinical value (Panda et al, ).…”

Section: Commentarymentioning

confidence: 99%

Antimicrobial resistance: A multifaceted problem with multipronged solutions

et al. 2019

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Infectious diseases still stand as a major cause of morbidity and mortality, and this problem can be worsened with the current antimicrobial resistance crisis. To tackle this crisis more studies analyzing the causes, routes, and reservoirs where antimicrobial resistance can emerge and expand, together with new antimicrobials and strategies for fighting antimicrobial resistance are needed. In the current special issue of MicrobiologyOpen, a set of articles dealing with the multiple faces of antimicrobial resistance are presented. These articles provide new information for understanding and addressing this problem.

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“…The Z‐ring, along with other regulatory proteins, forms a divisome complex, which regulates membrane constriction and peptidoglycan synthesis . FtsZ plays a central role in bacterial division and its inhibition arrests the bacterial cell division establishing FtsZ as a potential antibacterial target . The increasing resistance of the microbes to the existing antibacterial agents urges for the discovery of antibacterial agents with novel drug targets.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic insight into the effect of BT‐benzo‐29 on the Z‐ring in Bacillus subtilis

et al. 2020

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The assembly and disassembly of FtsZ play an essential role in bacterial cell division. Using single‐cell imaging, we report that short exposure to BT‐benzo‐29 inhibits Z‐ring formation in live Bacillus subtilis cells. Fluorescence recovery after photobleaching of the Z‐ring in live bacteria demonstrated that BT‐benzo‐29 strongly suppressed the assembly dynamics of FtsZ in the Z‐ring. Furthermore, B. subtilis cells expressing V275A‐FtsZ resisted the antibacterial activity of BT‐benzo‐29 providing evidence that BT‐benzo‐29 inhibits bacterial proliferation by targeting FtsZ. In addition, a brief (8 min) exposure of BT‐benzo‐29 destroyed the Z‐ring without perturbing the localization of a late cell division protein, DivIVA, the nucleoid segregation, and membrane permeability. BT‐benzo‐29, when used in combination with vancomycin and polymyxin B (PMB), produced a much stronger inhibitory effect on Bacillus subtilis and Escherichia coli cells, respectively. The combination index of BT‐benzo‐29 with vancomycin and PMB was determined to be <1, suggesting that BT‐benzo‐29 exhibits synergistic inhibitory effects on bacterial proliferation when used along with these antibiotics.

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Identification of Agents Targeting Ftsz Assembly

Cited by 29 publications

References 128 publications

An integrated computational-experimental approach reveals Yersinia pestis genes essential across a narrow or a broad range of environmental conditions

An integrated computational-experimental approach reveals Yersinia pestis genes essential across a narrow or a broad range of environmental conditions

Antimicrobial resistance: A multifaceted problem with multipronged solutions

Mechanistic insight into the effect of BT‐benzo‐29 on the Z‐ring in Bacillus subtilis

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