Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms

Slater, Ross T.; Frost, Lucy R.; Jossi, Sian; Millard, Andrew; Unnikrishnan, Meera

doi:10.1038/s41598-019-46143-6

Cited by 44 publications

(51 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pathogens likely release eDNA to help scavenge nutrients to survive. Similar importance of eDNA was also noted for Streptococcus intermedius (Petersen et al, 2004), Streptococcus mutans (Petersen et al, 2005), and Clostridioides difficile (Slater et al, 2019) biofilms.…”

Section: Edna In Gram-positive Bacteriasupporting

confidence: 67%

The role of extracellular DNA in the formation, architecture, stability, and treatment of bacterial biofilms

Panlilio

Rice

2021

Biotech & Bioengineering

View full text Add to dashboard Cite

Advances in biotechnology to treat and cure human disease have markedly improved human health and the development of modern societies. However, substantial challenges remain to overcome innate biological factors that thwart the activity and efficacy of pharmaceutical therapeutics. Until recently, the importance of extracellular DNA (eDNA) in biofilms was overlooked. New data reveal its extensive role in biofilm formation, adhesion, and structural integrity. Different approaches to target eDNA as anti-biofilm therapies have been proposed, but eDNA and the corresponding biofilm barriers are still difficult to disrupt. Therefore, more creative approaches to eradicate biofilms are needed. The production of eDNA often originates with the genetic material of bacterial cells through cell lysis.However, genomic DNA and eDNA are not necessarily structurally or compositionally identical. Variations are noteworthy because they dictate important interactions within the biofilm. Interactions between eDNA and biofilm components may as well be exploited as alternative anti-biofilm strategies. In this review, we discuss recent developments in eDNA research, emphasizing potential ways to disrupt biofilms. This review also highlights proteins, exopolysaccharides, and other molecules interacting with eDNA that can serve as anti-biofilm therapeutic targets.Overall, the array of diverse interactions with eDNA is important in biofilm structure, architecture, and stability. K E Y W O R D Santi-biofilm therapies, biofilms, eDNA, eDNA therapy, eDNA-interactions | BACKGROUNDA global health crisis is growing due to antibiotic resistance. Antibiotics were first prescribed to treat severe infections after Alexander Fleming discovered penicillin in the 1940's. Over time, various classes of antibiotics that target different bacterial machineries were introduced to the market. However, in recent years, the rate of discovery of new antibiotic classes has stagnated whereas the rate of antibiotic consumption has continued to increase (Silver, 2011). As a result, antibiotic resistance can emerge as bacteria respond to therapeutic treatments. The Centers for Disease Control and Prevention reports that at least 2.8 million people get infected and at least 35,000 die because of antibiotic resistant bacteria in the United States annually (CDC, 2019). In Europe, an estimated number of 25,000 deaths are associated to antibiotic resistant bacteria ("Annual report of the European Medicines Agency," 2010). Greater than 30,000 deaths per year are reported in countries like Thailand as well as increasing variants of antibiotic resistant bacteria emerging in South America, the Middle East, and Asia (Howell, 2013). In addition to these statistics, neonatal sepsis attributed to antibiotic resistance are increasing in Tanzania and Mozambique, and approximately 58,000 neonatal sepsis deaths related to antibiotic resistance are reported in India (Hellen et al., 2015

show abstract

Section: Edna In Gram-positive Bacteriasupporting

confidence: 67%

The role of extracellular DNA in the formation, architecture, stability, and treatment of bacterial biofilms

Panlilio

Rice

2021

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…Interestingly, C. difficile growth is negatively impacted when cocultured with Bacteroides dorei , an abundant gut commensal species (Figure 7). A reduction in C. difficile growth in presence of Bacteroides fragilis was reported previously 63 , appears to be less effective in reducing C. difficile growth compared to growth B. fragilis . Notably, B. fragilis much like B. dorei had higher numbers in mixed culture with C. difficile than it did on its own and growth inhibitory effects were specific to biofilm growth, indicating that cell-to-cell interactions/ physical proximity may play a role.…”

Section: Discussionmentioning

confidence: 62%

Dissecting individual pathogen-commensal interactions within a complex gut microbiota community

Hassall

Unnikrishnan

2020

Preprint

Self Cite

View full text Add to dashboard Cite

14Interactions of commensal bacteria within the gut microbiota and with invading pathogens 15 are critical in determining the outcome of an infection. While murine studies have been 16 valuable, we lack in vitro tools to monitor community responses to pathogens at a single-17 species level. We have developed a multi-species community of nine representative gut 18 species cultured together as a mixed biofilm and tracked numbers of individual species over 19 time using a qPCR-based approach. Introduction of the major nosocomial gut pathogen, 20Clostridiodes difficile, to this community resulted in increased adhesion of commensals and 21 inhibition of C. difficile multiplication. Interestingly, we observed an increase in individual 22Bacteroides species accompanying the inhibition of C. difficile. Furthermore, Bacteroides 23 dorei reduced C. difficile growth within biofilms, suggesting a role for Bacteroides spp in 24 prevention of C. difficile colonisation. We report here an in vitro tool with excellent 25 applications for investigating bacterial interactions within a complex community. 26 27 28 Disturbed microbiota and the loss of colonisation resistance are associated with several 49 pathogen infections including Clostridioides difficile 8 , Enterohemorrhagic E. coli 15 , and 50 Campylobacter jejuni 16 . 51 In the case of C. difficile, a leading cause of healthcare-associated diarrhoea worldwide, 52 colonisation occurs only when the microbiota is altered, usually due to treatment with 53 antibiotics such as fluoroquinolones 17 . The increased susceptibility of C. difficile infection (CDI) 54 after antibiotic-induced dysbiosis of the gut microbiota is well documented 18,19 . While most 55 4 studies demonstrating the link between CDI and antibiotic therapy are based on changes in 56 microbial populations by microbiota sequencing, recent studies have reported mechanisms by 57 which the microbiota can prevent C. difficile infections 20 . The microbiota in a healthy state 58 consumes or converts primary bile acid into secondary bile acids, reducing the ability of C. 59 difficile to germinate 21 . Secondary bile acids such as deoxycholic acid (DCA) and lithocholic 60 acid (LCA), are toxic to vegetative C. difficile 22,23 . Additionally, gut bacteria like Clostridium 61 scindens which encode secondary bile acid synthesis enzymes have been associated to 62 resistance to C. difficile infection 24 . The microbiota not only competes for resources but 63 actively inhibits C. difficile through production of bacteriocins such as the thuricin CD, 64 produced by Bacteroides thuringiensis 25 . 65While the microbiota is clearly important in preventing infections, current knowledge is mainly 66 based on microbiota profiles from faeces. The gut microbiota is composed of bacteria within 67 the lumen, which are usually detected in faeces and bacteria associated with the gut mucosa. 68Few studies have profiled the adherent microbiota population of healthy human guts as they 69 require invasive biopsies 26 . While not much is known abou...

show abstract

“…Bacteroides spp. can prevent C. difficile growth, both in vitro and in vivo; interestingly, B. fragilis appears to inhibit C. difficile only when in close contact within mixed biofilms, through an autoinducer-2-mediated mechanism [20]. In a culturomics study, 66 species isolated from microbiota were found to inhibit C. difficile.…”

Section: Difficile Interactions With the Microbiotamentioning

confidence: 99%

Clostridioides difficile biofilms: A mechanism of persistence in the gut?

2021

Self Cite

View full text Add to dashboard Cite

Biofilms are structured bacterial communities encased in an extracellular matrix. The structure and complexity of biofilms depend on the microorganism and the local environment [1,2]. Biofilms form on tissues and foreign implants during human infections and confer pathogens resistance to drugs and immune responses, making biofilm-associated infections extremely difficult to treat [1]. Clostridioides difficile, a major healthcare-associated gastrointestinal pathogen, causes C. difficile infection (CDI), which is associated with high rates of recurrence, especially in the elderly [3]. CDI is strongly associated with long-term antibiotic therapy, which results in disruption of the native gut microbiota. In recent years, C. difficile biofilms have been considered to be important for persistence of the bacterium in the gut and for recurrent infections. Here we review the current knowledge on C. difficile biofilms in the context of the gut environment and infection. C. difficile forms biofilms in vitro Biofilm formation by C. difficile was first reported by Donelli and colleagues where they identified the role of polymicrobial biofilms in clogging of biliary stents using confocal and field emission scanning electron microscopy [4]. Soon after, biofilm formation by C. difficile strains of clinical origin (strains 630, R20291) on abiotic surfaces was reported, as quantitated by crystal violet staining [5,6]. Viable cell counts, as well as LIVE/DEAD viability staining showed that bacterial viability was higher in 1-to 3-day-old biofilms and decreased in 6-day-old biofilms [4-7]. C. difficile biofilms are multilayered, encased in a thick matrix composed of bacterial proteins, extracellular DNA (eDNA), and polysaccharide II; however, it is noteworthy that the composition and structure of biofilms are both time-and strain-dependent [5,7]. Numerous C. difficile factors which modulate biofilm formation have been identified, including pili, flagella proteins, the S-layer, Cwp84, quorum sensing, germination receptor SleC, and sporulation. Mutants deficient in stress-related proteins including the SOS response regulator, LexA, the RNA chaperone, Hfq, and the heat stress-associated chaperone, DnaK, have been associated with increased biofilm formation [8-10]. Interestingly, the toxins TcdA and TcdB were identified in the biofilm matrix of 3-and 6-day-old biofilms, suggesting that biofilms may play a role in C. difficile virulence [7]. Cyclic di-GMP (c-di-GMP) is thought to play an important role in the motile to sessile biofilm state shift through repression of flagellar synthesis and induction of pili [11]. In a recent global gene expression analysis of microfermentor biofilms, several genes controlled by the SinR-like regulators CD2214 and CD2215, including pilA1, were differentially expressed in biofilms, although pilA1 appeared to contribute to biofilm/ aggregate formation only in c-di-GMP overexpressing strains [12]. Thus, C. difficile forms complex biofilms in vitro which involves multiple regulatory pathways and several vir...

show abstract

Clostridioides difficile LuxS mediates inter-bacterial interactions within biofilms

Cited by 44 publications

References 86 publications

The role of extracellular DNA in the formation, architecture, stability, and treatment of bacterial biofilms

The role of extracellular DNA in the formation, architecture, stability, and treatment of bacterial biofilms

Dissecting individual pathogen-commensal interactions within a complex gut microbiota community

Clostridioides difficile biofilms: A mechanism of persistence in the gut?

Contact Info

Product

Resources

About