Temporal proteomic profiling reveals changes that support Burkholderia biofilms

In the 1960s several groups reported the isolation and preliminary genetic mapping of Escherichia coli strains tolerant towards the action of colicins. These pioneering studies kick-started two new fields in bacteriology; one centred on how bacteriocins like colicins exploit the Tol (or more commonly Tol-Pal) system to kill bacteria, the other on the physiological role of this cell envelope-spanning assembly. The following half century has seen significant advances in the first of these fields whereas the second has remained elusive, until recently. Here, we review work that begins to shed light on Tol-Pal function in Gram-negative bacteria. What emerges from these studies is that Tol-Pal is an energised system with fundamental, interlinked roles in cell division – coordinating the re-structuring of peptidoglycan at division sites and stabilising the connection between the outer membrane and underlying cell wall. This latter role is achieved by Tol-Pal exploiting the proton motive force to catalyse the accumulation of the outer membrane peptidoglycan associated lipoprotein Pal at division sites while simultaneously mobilising Pal molecules from around the cell. These studies begin to explain the diverse phenotypic outcomes of tol-pal mutations, point to other cell envelope roles Tol-Pal may have and raise many new questions.

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“… 2016 ) with similar phenotypes reported for Burkholderia pseudomallei tolB (Khan et al . 2019 ) and E. coli tolA cells (Ranjith et al . 2019 ).…”

Section: Introductionmentioning

confidence: 99%

The multifarious roles of Tol-Pal in Gram-negative bacteria

Szczepaniak

Press

Kleanthous

2020

FEMS Microbiology Reviews

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“…In addition, bacteria prefer biofilm formation (multicellular communities of cells embedded in a self-produced extracellular matrix composed of polysaccharides, nucleic acids and proteins) as their primary growth mode, which provides the residing cells with higher chemotolerance in comparison to free-floating (planktonic) single cells, thus making infections notoriously hard to treat [ 4 , 5 ]. When adopting a biofilm lifestyle, bacteria change their genome and proteome in ways that contribute to their survival [ 6 , 7 ]. Many cellular mechanisms, involving, e.g., efflux pumps, the downregulation of key metabolic activities and switch to a dormant state, are contributory factors making the cells within the biofilm less susceptible to most antibiotics [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Screening of FDA-Approved Drugs Using a 384-Well Plate-Based Biofilm Platform: The Case of Fingolimod

et al. 2020

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In an effort to find new repurposed antibacterial compounds, we performed the screening of an FDA-approved compounds library against Staphylococcus aureus American Type Culture Collection (ATCC) 25923. Compounds were evaluated for their capacity to prevent both planktonic growth and biofilm formation as well as to disrupt pre-formed biofilms. One of the identified initial hits was fingolimod (FTY720), an immunomodulator approved for the treatment of multiple sclerosis, which was then selected for follow-up studies. Fingolimod displayed a potent activity against S. aureus and S. epidermidis with a minimum inhibitory concentration (MIC) within the range of 12–15 µM at which concentration killing of all the bacteria was confirmed. A time–kill kinetic study revealed that fingolimod started to drastically reduce the viable bacterial count within two hours and we showed that no resistance developed against this compound for up to 20 days. Fingolimod also displayed a high activity against Acinetobacter baumannii (MIC 25 µM) as well as a modest activity against Escherichia coli and Pseudomonas aeruginosa. In addition, fingolimod inhibited quorum sensing in Chromobacterium violaceum and might therefore target this signaling pathway in certain Gram-negative bacteria. In conclusion, we present the identification of fingolimod from a compound library and its evaluation as a potential repurposed antibacterial compound.

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“…[23,25,26]. Burkholderia species also produce and export numerous outer membrane polysaccharides and proteins [27][28][29]. Recent studies have suggested that biofilms can be dispersed by enzymes that target biofilm constituents [30].…”

Section: Introductionmentioning

confidence: 99%

Production and molecular composition of Burkholderia pseudomallei and Burkholderia thailandensis biofilms

Okaro

Mou

DeShazer

2021

Preprint

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Biofilm communities cause many infectious diseases. Biofilms are diverse microbial species found either attached to a surface or aggregated into an extracellular matrix. Bacteria form biofilms as a default mode of growth or as a response mechanism to environmental conditions like stress. As such, biofilm strains are increasingly virulent causing a wide variety of chronic persistent diseases, are typically antibiotic-resistant and known to improve host mortality rate. Most biofilms contain polysaccharides, proteins, extracellular DNA (eDNA), RNA, and water. Determining and quantifying the major components of a biofilm may indicate an appropriate treatment for biofilm eradication. Burkholderia pseudomallei is a Gram-negative, motile bacillus typically found in surface water and/or soil in endemic regions. It is the etiologic agent of melioidosis and is capable of forming both surface adherent and air-liquid interface biofilms (pellicle) in broth cultures. This study evaluates the components of established biofilms using B. pseudomallei and Burkholderia thailandensis, a closely related nonpathogenic species. Using assays, fluorescent dyes and microscopy, we quantified the major components of biofilms produced by five genetically related B. pseudomallei strains and compared them to B. thailandensis E264. Our data show that biofilm produced by the B. pseudomallei 1026b derivatives and B. thailandensis E264 significantly differ. The molecular composition of the surface adherent biofilm is similar to the molecular composition of the air-liquid pellicle. Finally, the eDNA quantity biofilm produced by JW270 which bears a CPS I deletion, is significantly increased in comparison to 1026 and Bp82 biofilm.

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Temporal proteomic profiling reveals changes that support Burkholderia biofilms

Cited by 12 publications

References 94 publications

The multifarious roles of Tol-Pal in Gram-negative bacteria

The multifarious roles of Tol-Pal in Gram-negative bacteria

Screening of FDA-Approved Drugs Using a 384-Well Plate-Based Biofilm Platform: The Case of Fingolimod

Production and molecular composition of Burkholderia pseudomallei and Burkholderia thailandensis biofilms

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