High frequency of blaPER-1 gene in clinical strains of Acinetobacter baumannii and its association with quorum sensing and virulence factors

Quorum sensing is a communication system based on the actions of chemical signal molecules depending on the density of the cell population. These molecules are widely considered as effectors of the gene expression of several virulence factors. As a result, it has attracted a lot of attention because of its possible applicability as a target for treating infections. This review attempts to give a description of this system on gram negative bacteria specifically on Acinetobacter baumannii as an important nosocomial pathogen. Additionally, quorum sensing in biofilm will be also treated because it is considered as the origin of several chronic infections. Numerous studies have been carried out to prove the role of inhibitors in the disruption of quorum sensing, known as quorum quenching. Quorum quenching is a new strategy to eradicate bacterial infections due to the crucial intervention of quorum sensing in different virulence factors and particularly in the biofilm formation.

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Faculty Opinions recommendation of A high-frequency phenotypic switch links bacterial virulence and environmental survival in Acinetobacter baumannii.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733089819.793547544 ◽

2018 ◽

Author(s):

Jan Roelof van der Meer ◽

Nicolas Carraro

Keyword(s):

Acinetobacter Baumannii ◽

High Frequency ◽

Bacterial Virulence ◽

Phenotypic Switch ◽

Environmental Survival

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Quorum Sensing – A Stratagem for Conquering Multi-Drug Resistant Pathogens

Current Pharmaceutical Design ◽

10.2174/1381612826666201210105638 ◽

2020 ◽

Vol 26 ◽

Author(s):

Madison Tonkin ◽

Shama Khan ◽

Mohmmad Younus Wani ◽

Aijaz Ahmad

Keyword(s):

Drug Resistance ◽

Quorum Sensing ◽

Virulence Factors ◽

Biofilm Formation ◽

Cell Communication ◽

Natural Compounds ◽

Quorum Sensing Inhibitors ◽

Communication Technique ◽

Multicellular Organisms ◽

Chemical Strategies

: Quorum sensing is defined as cell to cell communication between microorganisms, which enables microorganisms to behave as multicellular organisms. Quorum sensing enables many collaborative benefits such as synchronisation of virulence factors and biofilm formation. Both quorum sensing as well as biofilm formation encourage the development of drug resistance in microorganisms. Biofilm formation and quorum sensing are causally linked to each other and play role in the pathogenesis of microorganisms. With the increasing drug resistance against the available antibiotics and antifungal medications, scientists are combining different options to develop new strategies. Such strategies rely on the inhibition of the communication and virulence factors rather than on killing or inhibiting the growth of the microorganisms. This review encompasses the communication technique used by microorganisms, how microorganism resistance is linked to quorum sensing and various chemical strategies to combat quorum sensing and thereby drug resistance. Several compounds have been identified as quorum sensing inhibitors and are known to be effective in reducing resistance as they do not kill the pathogens but rather disrupt their communication. Natural compounds have been identified as anti-quorum sensing agents. However, natural compounds present several related disadvantages. Therefore, the need for the development of synthetic or semi-synthetic compounds has arisen. This review argues that anti-quorum sensing compounds are effective in disrupting quorum sensing and could therefore be effective in reducing microorganism drug resistance.

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Exploiting Quorum Sensing Inhibition for the Control of Pseudomonas aeruginosa and Acinetobacter baumannii Biofilms

Current Topics in Medicinal Chemistry ◽

10.2174/1568026617666170105144104 ◽

2017 ◽

Vol 17 (17) ◽

pp. 1915-1927 ◽

Cited By ~ 14

Author(s):

Israel Castillo-Juarez ◽

Luis Esau Lopez-Jacome ◽

Gloria Soberon-Chavez ◽

Maria Tomas ◽

Jintae Lee ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Acinetobacter Baumannii ◽

Quorum Sensing Inhibition

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Pseudomonas aeruginosa PA80 is a cystic fibrosis isolate deficient in RhlRI quorum sensing

Scientific Reports ◽

10.1038/s41598-021-85100-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Syed A. K. Shifat Ahmed ◽

Michelle Rudden ◽

Sabrina M. Elias ◽

Thomas J. Smyth ◽

Roger Marchant ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Virulence Factors ◽

Genomic Islands ◽

Clinical Strain ◽

Whole Genome ◽

Synonymous Mutations ◽

Wide Range

AbstractPseudomonas aeruginosa uses quorum sensing (QS) to modulate the expression of several virulence factors that enable it to establish severe infections. The QS system in P. aeruginosa is complex, intricate and is dominated by two main N-acyl-homoserine lactone circuits, LasRI and RhlRI. These two QS systems work in a hierarchical fashion with LasRI at the top, directly regulating RhlRI. Together these QS circuits regulate several virulence associated genes, metabolites, and enzymes in P. aeruginosa. Paradoxically, LasR mutants are frequently isolated from chronic P. aeruginosa infections, typically among cystic fibrosis (CF) patients. This suggests P. aeruginosa can undergo significant evolutionary pathoadaptation to persist in long term chronic infections. In contrast, mutations in the RhlRI system are less common. Here, we have isolated a clinical strain of P. aeruginosa from a CF patient that has deleted the transcriptional regulator RhlR entirely. Whole genome sequencing shows the rhlR locus is deleted in PA80 alongside a few non-synonymous mutations in virulence factors including protease lasA and rhamnolipid rhlA, rhlB, rhlC. Importantly we did not observe any mutations in the LasRI QS system. PA80 does not appear to have an accumulation of mutations typically associated with several hallmark pathoadaptive genes (i.e., mexT, mucA, algR, rpoN, exsS, ampR). Whole genome comparisons show that P. aeruginosa strain PA80 is closely related to the hypervirulent Liverpool epidemic strain (LES) LESB58. PA80 also contains several genomic islands (GI’s) encoding virulence and/or resistance determinants homologous to LESB58. To further understand the effect of these mutations in PA80 QS regulatory and virulence associated genes, we compared transcriptional expression of genes and phenotypic effects with isogenic mutants in the genetic reference strain PAO1. In PAO1, we show that deletion of rhlR has a much more significant impact on the expression of a wide range of virulence associated factors rather than deletion of lasR. In PA80, no QS regulatory genes were expressed, which we attribute to the inactivation of the RhlRI QS system by deletion of rhlR and mutation of rhlI. This study demonstrates that inactivation of the LasRI system does not impact RhlRI regulated virulence factors. PA80 has bypassed the common pathoadaptive mutations observed in LasR by targeting the RhlRI system. This suggests that RhlRI is a significant target for the long-term persistence of P. aeruginosa in chronic CF patients. This raises important questions in targeting QS systems for therapeutic interventions.

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Interaction of Acinetobacter baumannii with Human Serum Albumin: Does the Host Determines the Outcome?

Antibiotics ◽

10.3390/antibiotics10070833 ◽

2021 ◽

Vol 10 (7) ◽

pp. 833

Author(s):

Camila Pimentel ◽

Casin Le ◽

Marisel R. Tuttobene ◽

Tomas Subils ◽

Krisztina M. Papp-Wallace ◽

...

Keyword(s):

Antibiotic Resistance ◽

Human Serum Albumin ◽

Quorum Sensing ◽

Serum Albumin ◽

Human Serum ◽

Acinetobacter Baumannii ◽

Biofilm Formation ◽

Model Systems ◽

Expression Levels ◽

Multiple Drugs

Acinetobacter baumannii has become a serious threat to human health due to its extreme antibiotic resistance, environmental persistence, and capacity to survive within the host. Two A. baumannii strains, A118 and AB5075, commonly used as model systems, and three carbapenem-resistant strains, which are becoming ever more dangerous due to the multiple drugs they can resist, were exposed to 3.5% human serum albumin (HSA) and human serum (HS) to evaluate their response with respect to antimicrobial resistance, biofilm formation, and quorum sensing, all features responsible for increasing survival and persistence in the environment and human body. Expression levels of antibiotic resistance genes were modified differently when examined in different strains. The cmlA gene was upregulated or downregulated in conditions of exposure to 3.5% HSA or HS depending on the strain. Expression levels of pbp1 and pbp3 tended to be increased by the presence of HSA and HS, but the effect was not seen in all strains. A. baumannii A118 growing in the presence of HS did not experience increased expression of these genes. Aminoglycoside-modifying enzymes were also expressed at higher or lower levels in the presence of HSA or HS. Still, the response was not uniform; in some cases, expression was enhanced, and in other cases, it was tapered. While A. baumannii AB5075 became more susceptible to rifampicin in the presence of 3.5% HSA or HS, strain A118 did not show any changes. Expression of arr2, a gene involved in resistance to rifampicin present in A. baumannii AMA16, was expressed at higher levels when HS was present in the culture medium. HSA and HS reduced biofilm formation and production of N-Acyl Homoserine Lactone, a compound intimately associated with quorum sensing. In conclusion, HSA, the main component of HS, stimulates a variety of adaptative responses in infecting A. baumannii strains.

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Interference of quorum sensing regulated bacterial virulence factors and biofilms by Plumbago zeylanica extract

Microscopy Research and Technique ◽

10.1002/jemt.23872 ◽

2021 ◽

Author(s):

Faizan Abul Qais ◽

Iqbal Ahmad ◽

Fohad Mabood Husain ◽

Suliman Y. Alomar ◽

Naushad Ahmad ◽

...

Keyword(s):

Quorum Sensing ◽

Virulence Factors ◽

Bacterial Virulence ◽

Plumbago Zeylanica

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