Role of Bacterial Cytoskeleton and Other Apparatuses in Cell Communication

Singhi, Divya; Srivastava, Preeti

doi:10.3389/fmolb.2020.00158

Cited by 14 publications

(11 citation statements)

References 127 publications

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“…QS-dependant swarming and swimming motility of bacteria plays an important role during cell attachment, biofilm development, and dispersion [ 14 ]. It has been reported that the bacterial cytoskeletal proteins, especially MreB, play a fundamental role in cell communication by regulating QS signaling [ 61 ]. Notably, previous studies suggested that A22 could inhibit the swimming and swarming motility in P. aeruginosa PAO1 and Myxococcus xanthus [ 26 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Antibacterial and Antibiofilm Activity of the MreB Inhibitor A22 Hydrochloride in Combination with Conventional Antibiotics against Pseudomonas aeruginosa and Escherichia coli Clinical Isolates

Kotzialampou

Protonotariou

Skoura

et al. 2021

International Journal of Microbiology

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In the era of antibiotic resistance, the bacterial cytoskeletal protein MreB is presented as a potential target for the development of novel antimicrobials. Combined treatments of clinical antibiotics with anti-MreB compounds may be promising candidates in combating the resistance crisis, but also in preserving the potency of many conventional drugs. This study aimed to evaluate the synergistic antibacterial and antibiofilm activities of the MreB inhibitor A22 hydrochloride in combination with various antibiotics. The minimum inhibitory concentration (MIC) values of the individual compounds were determined by the broth microdilution method against 66 clinical isolates of Gram-negative bacteria. Synergy was assessed by the checkerboard assay. The fractional inhibitory concentration index was calculated for each of the A22-antibiotic combination. Bactericidal activity of the combinations was evaluated by time-kill curve assays. The antibiofilm activity of the most synergistic combinations was determined by crystal violet stain, methyl thiazol tetrazolium assay, and confocal laser scanning microscopy analysis. The combined cytotoxic and hemolytic activity was also evaluated toward human cells. According to our results, Pseudomonas aeruginosa and Escherichia coli isolates were resistant to conventional antibiotics to varying degrees. A22 inhibited the bacterial growth in a dose-dependent manner with MIC values ranging between 2 and 64 μg/mL. In combination studies, synergism occurred most frequently with A22-ceftazidime and A22-meropemen against Pseudomonas aeruginosa and A22-cefoxitin and A22-azithromycin against Escherichia coli. No antagonism was observed. In time-kill studies, synergism was observed with all expected combinations. Synergistic combinations even at the lowest tested concentrations were able to inhibit biofilm formation and eradicate mature biofilms in both strains. Cytotoxic and hemolytic effects of the same combinations toward human cells were not observed. The findings of the present study support previous research regarding the use of MreB as a novel antibiotic target. The obtained data expand the existing knowledge about the antimicrobial and antibiofilm activity of the A22 inhibitor, and they indicate that A22 can serve as a leading compound for studying potential synergism between MreB inhibitors and antibiotics in the future.

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Section: Discussionmentioning

confidence: 99%

Synergistic Antibacterial and Antibiofilm Activity of the MreB Inhibitor A22 Hydrochloride in Combination with Conventional Antibiotics against Pseudomonas aeruginosa and Escherichia coli Clinical Isolates

Kotzialampou

Protonotariou

Skoura

et al. 2021

International Journal of Microbiology

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“…34,35 Formally, FtsZ, Btub A/B, and eukaryotic tubulins form a separate family of GTPases. 36,37 They provide the earliest known division mechanism, the formation of a Z-ring located on the inner surface of the bacterial wall. Interestingly, the regulation of Z-ring formation is also used in the control of damage during delayed chromosome segregation or DNA damage.…”

Section: Introductionmentioning

confidence: 99%

“…Tubulin, on the other hand, has two additional large C-terminal helices that are located on the outer surface of the filaments and are considered the main site of interaction between motor proteins and other proteins that can associate with filaments. 36 One notable difference between FtsZ and tubulin has recently been shown to be in the kinetics of the GTPase reaction. 41,42 Tubulin hydrolyses GTP very quickly during polymerization, but the replacement of nucleotides in the protein itself is slow or absent.…”

Section: Introductionmentioning

confidence: 99%

Structure‐based virtual screening and biological evaluation of novel inhibitors of mycobacterium Z‐ring formation

Rayevsky

Dariya

Liudmyla

et al. 2022

J of Cellular Biochemistry

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The major part of commercial prodrugs against Mycobacterium tuberculosis (Mtb) demonstrated a significant inhibitory effect on cell division and inhibition of bacterial growth in vitro. However, further implementation often failed to overcome the compensatory system of interchangeable cascades. This is the most common situation for the compounds, which hit the key enzymes activities involved in all basic stages of the cell cycle. We decided to find more compounds, which could affect a cytoskeleton complex playing important role in sensing the external signals, intracellular transport, and cell division. In general, the bacterial cytoskeleton is crucial for response to the environment and participates in cell-to-cell communication. In turn, filamentous temperature-sensitive Z (FtsZ) protein, a mycobacterial tubulin homolog, is essential for Z-ring formation and further bacteria cell division. We predicted the most preferable binding-sites and conducted a highthroughput virtual screening. Modeling results suggest that some compounds bind in a specific region on the surface Mtb FtsZ, which is absent in human, and other could hit GTPase activity of the FtsZ. Further in vitro studies confirmed that these novel molecules can efficiently bind to these pockets, demonstrating an effect on the polymerization state and kinetics mechanisms.The rescaling of the experiment on the cell line revealed that reported

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“…Although to date (as of 28 July 2020) there have been no observations of ADE in antibodies currently in clinical trials for COVID-19 [ 107 ], in vitro and in vivo studies, as well as two early clinical studies in China, showed that patients with severe disease frequently had an increased IgG response [ 108. , 109. , 110.…”

Section: Challenges In the Successful Development Of Neutralizing Antmentioning

confidence: 99%

Fruitful Neutralizing Antibody Pipeline Brings Hope To Defeat SARS-Cov-2

Renn

et al. 2020

Trends in Pharmacological Sciences

114

129

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With the recent spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2)_ infecting >16 million people worldwide as of 28 July 2020, causing >650 000 deaths, there is a desperate need for therapeutic agents and vaccines. Building on knowledge of previous outbreaks of SARS-CoV-1 and Middle East respiratory syndrome (MERS), the development of therapeutic antibodies and vaccines against coronavirus disease 2019 (COVID-19) is taking place at an unprecedented speed. Current efforts towards the development of neutralizing antibodies against COVID-19 are summarized. We also highlight the importance of a fruitful antibody development pipeline to combat the potential escape plans of SARS-CoV-2, including somatic mutations and antibody-dependent enhancement (ADE).

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Role of Bacterial Cytoskeleton and Other Apparatuses in Cell Communication

Cited by 14 publications

References 127 publications

Synergistic Antibacterial and Antibiofilm Activity of the MreB Inhibitor A22 Hydrochloride in Combination with Conventional Antibiotics against Pseudomonas aeruginosa and Escherichia coli Clinical Isolates

Synergistic Antibacterial and Antibiofilm Activity of the MreB Inhibitor A22 Hydrochloride in Combination with Conventional Antibiotics against Pseudomonas aeruginosa and Escherichia coli Clinical Isolates

Structure‐based virtual screening and biological evaluation of novel inhibitors of mycobacterium Z‐ring formation

Fruitful Neutralizing Antibody Pipeline Brings Hope To Defeat SARS-Cov-2

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