scholarly journals Bacteriophage Adherence to Mucus Mediates Preventive Protection against Pathogenic Bacteria

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Gabriel M. F. Almeida ◽  
Elina Laanto ◽  
Roghaieh Ashrafi ◽  
Lotta-Riina Sundberg
Keyword(s):  
Disease Ecology ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Bacterial Virulence ◽  
Model Systems ◽  
Symbiotic Relationship ◽  
Content Type ◽  
Ecological Benefit ◽  
Mucosal Surfaces

ABSTRACT Metazoans were proposed to host bacteriophages on their mucosal surfaces in a symbiotic relationship, where phages provide an external immunity against bacterial infections and the metazoans provide phages a medium for interacting with bacteria. However, scarce empirical evidence and model systems have left the phage-mucus interaction poorly understood. Here, we show that phages bind both to porcine mucus and to rainbow trout (Oncorhynchus mykiss) primary mucus, persist up to 7 days in the mucosa, and provide protection against Flavobacterium columnare. Also, exposure to mucus changes the bacterial phenotype by increasing bacterial virulence and susceptibility to phage infections. This trade-off in bacterial virulence reveals ecological benefit of maintaining phages in the metazoan mucosal surfaces. Tests using other phage-bacterium pairs suggest that phage binding to mucus may be widespread in the biosphere, indicating its importance for disease, ecology, and evolution. This phenomenon may have significant potential to be exploited in preventive phage therapy. IMPORTANCE The mucosal surfaces of animals are habitat for microbes, including viruses. Bacteriophages—viruses that infect bacteria—were shown to be able to bind to mucus. This may result in a symbiotic relationship in which phages find bacterial hosts to infect, protecting the mucus-producing animal from bacterial infections in the process. Here, we studied phage binding on mucus and the effect of mucin on phage-bacterium interactions. The significance of our research is in showing that phage adhesion to mucus results in preventive protection against bacterial infections, which will serve as basis for the development of prophylactic phage therapy approaches. Besides, we also reveal that exposure to mucus upregulates bacterial virulence and that this is exploited by phages for infection, adding one additional layer to the metazoan-bacterium-phage biological interactions and ecology. This phenomenon might be widespread in the biosphere and thus crucial for understanding mucosal diseases, their outcome and treatment.

scholarly journals Bacteriophage adherence to mucus mediates preventive protection against pathogenic bacteria

2019 ◽  
Author(s):  
Gabriel MF Almeida ◽  
Elina Laanto ◽  
Roghaieh Ashrafi ◽  
Lotta-Riina Sundberg
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Bacterial Virulence ◽  
Model Systems ◽  
Symbiotic Relationship ◽  
Flavobacterium Columnare ◽  
Ecological Interactions ◽  
Fish Pathogen ◽  
Mucosal Surfaces

AbstractMetazoan mucosal surfaces are major interfaces between the organism and environment. These surfaces have been proposed to host bacteriophages in a symbiotic relationship with metazoans. Considering the so far poorly understood phage–mucus interaction and its role in ecological interactions and for mucosal bacterial infections, empirical evidence and model systems need to be established. Here, using the fish pathogenFlavobacterium columnareand rainbow trout (Oncorhynchus mykiss), we show that phages infecting the pathogen are capable of binding to primary mucus layers and protecting fish from infections. Furthermore, exposure to mucus changes the bacterial phenotype by increasing bacterial virulence and susceptibility to phage infections. Tests using other phage–bacterium pairs suggest that the relevance of mucus for bacteria and phages may be widespread in the biosphere. Therefore, interactions of bacteria and phages inside the mucus environment may be important for disease and evolution, and this phenomenon has significant potential to be exploited for preventive phage therapy approaches.

scholarly journals Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria

2017 ◽  
Vol 63 (11) ◽  
pp. 865-879 ◽  
Author(s):  
Ayman El-Shibiny ◽  
Salma El-Sahhar
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Multidrug Resistant ◽  
Clinical Applications ◽  
Western World ◽  
Resistant Bacteria ◽  
Vaccine Production ◽  
Bacterial Populations ◽  
Antibiotic Resistant

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.

scholarly journals Disruption of VirB6 Paralogs in Anaplasma phagocytophilum Attenuates Its Growth

2020 ◽  
Vol 202 (23) ◽  
Author(s):  
Francy L. Crosby ◽  
Ulrike G. Munderloh ◽  
Curtis M. Nelson ◽  
Michael J. Herron ◽  
Anna M. Lundgren ◽  
...  
Keyword(s):  
Anaplasma Phagocytophilum ◽  
Pathogenic Bacteria ◽  
Tandem Repeats ◽  
Model Systems ◽  
Accession Number ◽  
Secretion Systems ◽  
Altered Expression ◽  
Content Type ◽  
Obligate Intracellular

ABSTRACT Many pathogenic bacteria translocate virulence factors into their eukaryotic hosts by means of type IV secretion systems (T4SS) spanning the inner and outer membranes. Genes encoding components of these systems have been identified within the order Rickettsiales based upon their sequence similarities to other prototypical systems. Anaplasma phagocytophilum strains are obligate intracellular, tick-borne bacteria that are members of this order. The organization of these components at the genomic level was determined in several Anaplasma phagocytophilum strains, showing overall conservation, with the exceptions of the virB2 and virB6 genes. The virB6 loci are characterized by the presence of four virB6 copies (virB6-1 through virB6-4) arranged in tandem within a gene cluster known as the sodB-virB operon. Interestingly, the virB6-4 gene varies significantly in length among different strains due to extensive tandem repeats at the 3′ end. To gain an understanding of how these enigmatic virB6 genes function in A. phagocytophilum, we investigated their expression in infected human and tick cells. Our results show that these genes are expressed by A. phagocytophilum replicating in both cell types and that VirB6-3 and VirB6-4 proteins are surface exposed. Analysis of an A. phagocytophilum mutant carrying the Himar1 transposon within the virB6-4 gene demonstrated that the insertion not only disrupted its expression but also exerted a polar effect on the sodB-virB operon. Moreover, the altered expression of genes within this operon was associated with the attenuated in vitro growth of A. phagocytophilum in human and tick cells, indicating the importance of these genes in the physiology of this obligate intracellular bacterium in such different environments. IMPORTANCE Knowledge of the T4SS is derived from model systems, such as Agrobacterium tumefaciens. The structure of the T4SS in Rickettsiales differs from the classical arrangement. These differences include missing and duplicated components with structural alterations. Particularly, two sequenced virB6-4 genes encode unusual C-terminal structural extensions resulting in proteins of 4,322 (GenBank accession number AGR79286.1) and 9,935 (GenBank accession number ANC34101.1>) amino acids. To understand how the T4SS is used in A. phagocytophilum, we describe the expression of the virB6 paralogs and explore their role as the bacteria replicate within its host cell. Conclusions about the importance of these paralogs for colonization of human and tick cells are supported by the deficient phenotype of an A. phagocytophilum mutant isolated from a sequence-defined transposon insertion library.

scholarly journals Characterization and Genomic Analysis of ValSw3-3, a New Siphoviridae Bacteriophage Infecting Vibrio alginolyticus

2020 ◽  
Vol 94 (10) ◽  
Author(s):  
Ling Chen ◽  
Quan Liu ◽  
Jiqiang Fan ◽  
Tingwei Yan ◽  
Haoran Zhang ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
In Silico ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Gc Content ◽  
Vibrio Alginolyticus ◽  
Lytic Bacteriophage ◽  
Sequence Alignments ◽  
Content Type ◽  
Link Type

ABSTRACT A novel lytic bacteriophage, ValSw3-3, which efficiently infects pathogenic strains of Vibrio alginolyticus, was isolated from sewage water and characterized by microbiological and in silico genomic analyses. Transmission electron microscopy indicated that ValSw3-3 has the morphology of siphoviruses. This phage can infect four species in the Vibrio genus and has a latent period of 15 min and a burst size of 95 ± 2 PFU/infected bacterium. Genome sequencing results show that ValSw3-3 has a 39,846-bp double-stranded DNA genome with a GC content of 43.1%. The similarity between the genome sequences of ValSw3-3 and those of other phages recorded in the GenBank database was below 50% (42%), suggesting that ValSw3-3 significantly differs from previously reported phages at the DNA level. Multiple genome comparisons and phylogenetic analysis based on the major capsid protein revealed that phage ValSw3-3 is grouped in a clade with five other phages, including Listonella phage phiHSIC (GenBank accession no. NC_006953.1), Vibrio phage P23 (MK097141.1), Vibrio phage pYD8-B (NC_021561.1), Vibrio phage 2E1 (KX507045.1), and Vibrio phage 12G5 (HQ632860.1), and is distinct from all known genera within the Siphoviridae family that have been ratified by the International Committee on Taxonomy of Viruses (ICTV). An in silico proteomic comparison of diverse phages from the Siphoviridae family supported this clustering result and suggested that ValSw3-3, phiHSIC, P23, pYD8-B, 2E1, and 12G5 should be classified as a novel genus cluster of Siphoviridae. A subsequent analysis of core genes also revealed the common genes shared within this new cluster. Overall, these results provide a characterization of Vibrio phage ValSw3-3 and support our proposal of a new viral genus within the family Siphoviridae. IMPORTANCE Phage therapy has been considered a potential alternative to antibiotic therapy in treating bacterial infections. For controlling the vibriosis-causing pathogen Vibrio alginolyticus, well-documented phage candidates are still lacking. Here, we characterize a novel lytic Vibrio phage, ValSw3-3, based on its morphology, host range and infectivity, growth characteristics, stability under various conditions, and genomic features. Our results show that ValSw3-3 could be a potent candidate for phage therapy to treat V. alginolyticus infections due to its stronger infectivity and better pH and thermal stability than those of previously reported Vibrio phages. Moreover, genome sequence alignments, phylogenetic analysis, in silico proteomic comparison, and core gene analysis all support that this novel phage, ValSw3-3, and five unclassified phages form a clade distant from those of other known genera ratified by the ICTV. Thus, we propose a new viral genus within the Siphoviridae family to accommodate this clade, with ValSw3-3 as a representative member.

scholarly journals Effects of Sequential and Simultaneous Applications of Bacteriophages on Populations of Pseudomonas aeruginosaIn Vitroand in Wax Moth Larvae

2012 ◽  
Vol 78 (16) ◽  
pp. 5646-5652 ◽  
Author(s):  
Alex R. Hall ◽  
Daniel De Vos ◽  
Ville-Petri Friman ◽  
Jean-Paul Pirnay ◽  
Angus Buckling
Keyword(s):  
Bacterial Infections ◽  
Phage Therapy ◽  
Phage Type ◽  
Resistant Bacteria ◽  
Short Term ◽  
Short Term Treatment ◽  
Simultaneous Application ◽  
Content Type ◽  
Wax Moth

ABSTRACTInterest in using bacteriophages to treat bacterial infections (phage therapy) is growing, but there have been few experiments comparing the effects of different treatment strategies on both bacterial densities and resistance evolution. While it is established that multiphage therapy is typically more effective than the application of a single phage type, it is not clear if it is best to apply phages simultaneously or sequentially. We tried single- and multiphage therapy againstPseudomonas aeruginosaPAO1in vitro, using different combinations of phages either simultaneously or sequentially. Across different phage combinations, simultaneous application was consistently equal or superior to sequential application in terms of reducing bacterial population density, and there was no difference (on average) in terms of minimizing resistance. Phage-resistant bacteria emerged in all experimental treatments and incurred significant fitness costs, expressed as reduced growth rate in the absence of phages. Finally, phage therapy increased the life span of wax moth larvae infected withP. aeruginosa, and a phage cocktail was the most effective short-term treatment. When the ratio of phages to bacteria was very high, phage cocktails cured otherwise lethal infections. These results suggest that while adding all available phages simultaneously tends to be the most successful short-term strategy, there are sequential strategies that are equally effective and potentially better over longer time scales.

scholarly journals The Concerted Action of Two B3-Like Prophage Genes Excludes Superinfecting Bacteriophages by Blocking DNA Entry into Pseudomonas aeruginosa

2020 ◽  
Vol 94 (15) ◽  
Author(s):  
Marco Antonio Carballo-Ontiveros ◽  
Adrián Cazares ◽  
Pablo Vinuesa ◽  
Luis Kameyama ◽  
Gabriel Guarneros
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pathogenic Bacteria ◽  
Phage Therapy ◽  
Alternative Therapy ◽  
Multidrug Resistant ◽  
Open Reading Frames ◽  
Resistant Bacteria ◽  
Content Type ◽  
Secondary Infections ◽  
Genes Encoding

ABSTRACT In this study, we describe seven vegetative phage genomes homologous to the historic phage B3 that infect Pseudomonas aeruginosa. Like other phage groups, the B3-like group contains conserved (core) and variable (accessory) open reading frames (ORFs) grouped at fixed regions in their genomes; however, in either case, many ORFs remain without assigned functions. We constructed lysogens of the seven B3-like phages in strain Ps33 of P. aeruginosa, a novel clinical isolate, and assayed the exclusion phenotype against a variety of temperate and virulent superinfecting phages. In addition to the classic exclusion conferred by the phage immunity repressor, the phenotype observed in B3-like lysogens suggested the presence of other exclusion genes. We set out to identify the genes responsible for this exclusion phenotype. Phage Ps56 was chosen as the study subject since it excluded numerous temperate and virulent phages. Restriction of the Ps56 genome, cloning of several fragments, and resection of the fragments that retained the exclusion phenotype allowed us to identify two core ORFs, so far without any assigned function, as responsible for a type of exclusion. Neither gene expressed separately from plasmids showed activity, but the concurrent expression of both ORFs is needed for exclusion. Our data suggest that phage adsorption occurs but that phage genome translocation to the host’s cytoplasm is defective. To our knowledge, this is the first report on this type of exclusion mediated by a prophage in P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa is a Gram-negative bacterium frequently isolated from infected immunocompromised patients, and the strains are resistant to a broad spectrum of antibiotics. Recently, the use of phages has been proposed as an alternative therapy against multidrug-resistant bacteria. However, this approach may present various hurdles. This work addresses the problem that pathogenic bacteria may be lysogenized by phages carrying genes encoding resistance against secondary infections, such as those used in phage therapy. Discovering phage genes that exclude superinfecting phages not only assigns novel functions to orphan genes in databases but also provides insight into selection of the proper phages for use in phage therapy.

scholarly journals Potentiation of Tobramycin by Silver Nanoparticles against Pseudomonas aeruginosa Biofilms

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Marc B. Habash ◽  
Mara C. Goodyear ◽  
Amber J. Park ◽  
Matthew D. Surette ◽  
Emily C. Vis ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Silver Nanoparticles ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Acute Infection ◽  
Public Health Problem ◽  
Chronic Infections ◽  
Content Type

ABSTRACT Increasing antibiotic resistance among pathogenic bacterial species is a serious public health problem and has prompted research examining the antibacterial effects of alternative compounds and novel treatment strategies. Compounding this problem is the ability of many pathogenic bacteria to form biofilms during chronic infections. Importantly, these communities are often recalcitrant to antibiotic treatments that show effectiveness against acute infection. The antimicrobial properties of silver have been known for decades, but recently silver and silver-containing compounds have seen renewed interest as antimicrobial agents for treating bacterial infections. The goal of this study was to assess the ability of citrate-capped silver nanoparticles (AgNPs) of various sizes, alone and in combination with the aminoglycoside antibiotic tobramycin, to inhibit established Pseudomonas aeruginosa biofilms. Our results demonstrate that smaller 10-nm and 20-nm AgNPs were more effective at synergistically potentiating the activity of tobramycin. Visualization of biofilms treated with combinations of 10-nm AgNPs and tobramycin reveals that the synergistic bactericidal effect may be caused by disrupting cellular membranes. Minimum biofilm eradication concentration (MBEC) assays using clinical P. aeruginosa isolates shows that small AgNPs are more effective than larger AgNPs at inhibiting biofilms, but that the synergy effect is likely a strain-dependent phenomenon. These data suggest that small AgNPs synergistically potentiate the activity of tobramycin against P. aeruginosa in vitro and may reveal a potential role for AgNP/antibiotic combinations in treating patients with chronic infections in a strain-specific manner.

scholarly journals Residual Antibiotics Disrupt Meat Fermentation and Increase Risk of Infection

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Jette Kjeldgaard ◽  
Marianne T. Cohn ◽  
Pat G. Casey ◽  
Colin Hill ◽  
Hanne Ingmer
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Starter Cultures ◽  
Farm Animals ◽  
Veterinary Antibiotics ◽  
Growth Promoters ◽  
Content Type ◽  
Fermented Sausages ◽  
Serovar Typhimurium ◽  
Meat Fermentation

ABSTRACTFermented sausages, although presumed safe for consumption, sometimes cause serious bacterial infections in humans that may be deadly. Not much is known about why and when this is the case. We tested the hypothesis that residual veterinary antibiotics in meat can disrupt the fermentation process, giving pathogenic bacteria a chance to survive and multiply. We found that six commercially available starter cultures were susceptible to commonly used antibiotics, namely, oxytetracycline, penicillin, and erythromycin. In meat, statutorily tolerable levels of oxytetracycline and erythromycin inhibited fermentation performance of three and five of the six starter cultures, respectively. In model sausages, the disruption of meat fermentation enhanced survival of the pathogensEscherichia coliO157:H7 andSalmonella entericaserovar Typhimurium compared to successful fermentations. Our work reveals an overlooked risk associated with the presence of veterinary drugs in meat.IMPORTANCEAntibiotics have for a long time been used as growth promoters in farm animals, and while they are banned as such in Europe, their clinical use in farm animals still accounts for the majority of consumption. Here, we examined how acceptable levels of antibiotics in meat influence fermentation. Our results show that commonly used bacterial starter cultures are sensitive to residual antibiotics at or near statutorily tolerable levels, and as a result, processed sausages may indeed contain high levels of pathogens. Our findings provide a possible explanation for outbreaks and disease cases associated with consumption of fermented sausages and offer yet another argument for limiting the use of antimicrobials in farm animals.

scholarly journals UVC Light Prophylaxis for Cutaneous Wound Infections in Mice

2012 ◽  
Vol 56 (7) ◽  
pp. 3841-3848 ◽  
Author(s):  
Tianhong Dai ◽  
Barbara Garcia ◽  
Clinton K. Murray ◽  
Mark S. Vrahas ◽  
Michael R. Hamblin
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Light Exposure ◽  
Dna Lesions ◽  
Bacterial Cells ◽  
Wound Infections ◽  
Content Type ◽  
Cutaneous Wound ◽  
Thickness Skin

ABSTRACTUVC light has long been known to be highly germicidal but has not been much developed as a therapy for infections. This study investigated the potential of UVC light for the prophylaxis of infections developing in highly contaminated superficial cutaneous wounds.In vitrostudies demonstrated that the pathogenic bacteriaPseudomonas aeruginosaandStaphylococcus aureuswere inactivated at UVC light exposures much lower than those needed for a similar effect on mammalian keratinocytes. Mouse models of partial-thickness skin abrasions infected with bioluminescentP. aeruginosaandS. aureuswere developed. Approximately 107bacterial cells were inoculated onto wounds measuring 1.2 by1.2 cm on the dorsal surfaces of mice. UVC light was delivered at 30 min after bacterial inoculation. It was found that for both bacterial infections, UVC light at a single radiant exposure of 2.59 J/cm2reduced the bacterial burden in the infected mouse wounds by approximately 10-fold in comparison to those in untreated mouse wounds (P< 0.00001). Furthermore, UVC light increased the survival rate of mice infected withP. aeruginosaby 58.3% (P= 0.0023) and increased the wound healing rate in mice infected withS. aureusby 31.2% (P< 0.00001). DNA lesions were observed in the UVC light-treated mouse wounds; however, the lesions were extensively repaired by 48 h after UVC light exposure. These results suggested that UVC light may be used for the prophylaxis of cutaneous wound infections.

scholarly journals Identification of Quorum-Sensing Inhibitors Disrupting Signaling between Rgg and Short Hydrophobic Peptides in Streptococci

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Chaitanya Aggarwal ◽  
Juan Cristobal Jimenez ◽  
Hyun Lee ◽  
George E. Chlipala ◽  
Kiira Ratia ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Communication Networks ◽  
Drug Targets ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Chemical Compounds ◽  
Content Type ◽  
Hydrophobic Peptides ◽  
Biofilm Development

ABSTRACTBacteria coordinate a variety of social behaviors, important for both environmental and pathogenic bacteria, through a process of intercellular chemical signaling known as quorum sensing (QS). As microbial resistance to antibiotics grows more common, a critical need has emerged to develop novel anti-infective therapies, such as an ability to attenuate bacterial pathogens by means of QS interference. Rgg quorum-sensing pathways, widespread in the phylumFirmicutes, employ cytoplasmic pheromone receptors (Rgg transcription factors) that directly bind and elicit gene expression responses to imported peptide signals. In the human-restricted pathogenStreptococcus pyogenes, the Rgg2/Rgg3 regulatory circuit controls biofilm development in response to the short hydrophobic peptides SHP2 and SHP3. Using Rgg-SHP as a model receptor-ligand target, we sought to identify chemical compounds that could specifically inhibit Rgg quorum-sensing circuits. Individual compounds from a diverse library of known drugs and drug-like molecules were screened for their ability to disrupt complexes of Rgg and FITC (fluorescein isothiocyanate)-conjugated SHP using a fluorescence polarization (FP) assay. The best hits were found to bind Rgg3in vitrowith submicromolar affinities, to specifically abolish transcription of Rgg2/3-controlled genes, and to prevent biofilm development inS. pyogeneswithout affecting bacterial growth. Furthermore, the top hit, cyclosporine A, as well as its nonimmunosuppressive analog, valspodar, inhibited Rgg-SHP pathways in multiple species ofStreptococcus. The Rgg-FITC-peptide-based screen provides a platform to identify inhibitors specific for each Rgg type. Discovery of Rgg inhibitors constitutes a step toward the goal of manipulating bacterial behavior for purposes of improving health.IMPORTANCEThe global emergence of antibiotic-resistant bacterial infections necessitates discovery not only of new antimicrobials but also of novel drug targets. Since antibiotics restrict microbial growth, strong selective pressures to develop resistance emerge quickly in bacteria. A new strategy to fight microbial infections has been proposed, namely, development of therapies that decrease pathogenicity of invading organisms while not directly inhibiting their growth, thus decreasing selective pressure to establish resistance. One possible means to this goal is to interfere with chemical communication networks used by bacteria to coordinate group behaviors, which can include the synchronized expression of genes that lead to disease. In this study, we identified chemical compounds that disrupt communication pathways regulated by Rgg proteins in species ofStreptococcus. Treatment of cultures ofS. pyogeneswith the inhibitors diminished the development of biofilms, demonstrating an ability to control bacterial behavior with chemicals that do not inhibit growth.

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