Exploiting cooperative pathogen behaviour for enhanced antibiotic potency: A Trojan horse approach.

Antimicrobial resistance poses an escalating global threat, rendering traditional drug development approaches increasingly ineffective. Thus, novel alternatives to antibiotic-based therapies are needed. Exploiting pathogen cooperation as a strategy for combating resistant infections has been proposed but lacks experimental validation.

Lipid A Structural Variants Induce Altered Immune Responses.

causes chronic lung infection in cystic fibrosis (CF), resulting in structural lung damage and progressive pulmonary decline. in the CF lung undergoes numerous changes, adapting to host-specific airway pressures while establishing chronic infection. undergoes lipid A structural modification during CF chronic infection that is not seen in any other disease state.

The role of hypermutation and collateral sensitivity in antimicrobial resistance diversity of populations in cystic fibrosis lung infection.

is an opportunistic pathogen which causes chronic, drug-resistant lung infections in cystic fibrosis (CF) patients. In this study, we explore the role of genomic diversification and evolutionary trade-offs in antimicrobial resistance (AMR) diversity within populations sourced from CF lung infections. We analyzed 300 clinical isolates from four CF patients (75 per patient) and found that genomic diversity is not a consistent indicator of phenotypic AMR diversity.

Exploiting Cooperative Pathogen Behavior for Enhanced Antibiotic Potency: A Trojan Horse Approach.

Antimicrobial resistance poses an escalating global threat, rendering traditional drug development approaches increasingly ineffective. Thus, novel alternatives to antibiotic-based therapies are needed. Exploiting pathogen cooperation as a strategy for combating resistant infections has been proposed but lacks experimental validation.

High prevalence of lipopolysaccharide mutants and R2-pyocin susceptible variants in populations sourced from cystic fibrosis lung infections.

Cystic fibrosis (CF) patients often experience chronic, debilitating lung infections caused by antibiotic-resistant , contributing to antimicrobial resistance (AMR). The genetic and phenotypic diversity of populations in CF lungs raises questions about their susceptibility to non-traditional antimicrobials, like bacteriocins. In this study, we focused on R-pyocins, a type of bacteriocin with high potency and a narrow killing spectrum.

Microbial Primer: LuxR-LuxI Quorum Sensing.

Quorum sensing is a term describing bacterial cell-to-cell communication systems for monitoring and responding to changes in population density. This primer serves as an introduction to the canonical LuxR-LuxI-type quorum sensing circuits common to many species of Gram-negative bacteria. Quorum sensing can synchronize behaviours across a community.

The Role of Hypermutation and Collateral Sensitivity in Antimicrobial Resistance Diversity of Populations in Cystic Fibrosis Lung Infection.

is an opportunistic pathogen which causes chronic, drug-resistant lung infections in cystic fibrosis (CF) patients. In this study, we explore the role of genomic diversification and evolutionary trade-offs in antimicrobial resistance (AMR) diversity within populations sourced from CF lung infections. We analyzed 300 clinical isolates from four CF patients (75 per patient), and found that genomic diversity is not a consistent indicator of phenotypic AMR diversity.

High prevalence of lipopolysaccharide mutants and R2-Pyocin susceptible variants in populations sourced from cystic fibrosis lung infections.

Chronic, highly antibiotic-resistant infections in cystic fibrosis (CF) lungs contribute to increasing morbidity and mortality. , a common CF pathogen, exhibits resistance to multiple antibiotics, contributing to antimicrobial resistance (AMR). These bacterial populations display genetic and phenotypic diversity, but it is unclear how this diversity affects susceptibility to bacteriocins.

Frequency of quorum-sensing mutations in strains isolated from different environments.

uses quorum sensing (QS) to coordinate the expression of multiple genes necessary for establishing and maintaining infection. It has previously been shown that QS mutations frequently arise in cystic fibrosis (CF) lung infections, however, there has been far less emphasis on determining whether other QS system mutations arise during infection or in other environments. To test this, we utilized 852 publicly available sequenced genomes from the International Consortium Database (IPCD) to study QS mutational signatures.

strain degeneration is driven by the loss of Spo0A activity.

Solventogenic clostridia represent a diverse group of anaerobic, spore-forming bacteria capable of producing acetone, butanol and ethanol through their unique biphasic metabolism. An intrinsic problem with these organisms however is their tendency to degenerate when repeatedly subcultured or when grown continuously. This phenomenon sees cells lose their ability to produce solvents and spores, posing a significant problem for industrial applications.

O-Specific Antigen-Dependent Surface Hydrophobicity Mediates Aggregate Assembly Type in Pseudomonas aeruginosa.

Bacteria live in spatially organized aggregates during chronic infections, where they adapt to the host environment, evade immune responses, and resist therapeutic interventions. Although it is known that environmental factors such as polymers influence bacterial aggregation, it is not clear how bacterial adaptation during chronic infection impacts the formation and spatial organization of aggregates in the presence of polymers. Here, we show that in an model of cystic fibrosis (CF) containing the polymers extracellular DNA (eDNA) and mucin, O-specific antigen is a major factor determining the formation of two distinct aggregate assembly types of Pseudomonas aeruginosa due to alterations in cell surface hydrophobicity.

Heterogenous Susceptibility to R-Pyocins in Populations of Pseudomonas aeruginosa Sourced from Cystic Fibrosis Lungs.

Bacteriocins are proteinaceous antimicrobials produced by bacteria that are active against other strains of the same species. R-type pyocins are phage tail-like bacteriocins produced by Due to their antipseudomonal activity, R-pyocins have potential as therapeutics in infection. is a Gram-negative opportunistic pathogen and is particularly problematic for individuals with cystic fibrosis (CF).

The evolution of virulence in during chronic wound infection.

Opportunistic pathogens are associated with a number of chronic human infections, yet the evolution of virulence in these organisms during chronic infection remains poorly understood. Here, we tested the evolution of virulence in the human opportunistic pathogen in a murine chronic wound model using a two-part serial passage and sepsis experiment, and found that virulence evolved in different directions in each line of evolution. We also assessed adaptation to a chronic wound after 42 days of evolution and found that morphological diversity in our evolved populations was limited compared with that previously described in cystic fibrosis (CF) infections.

Bacterial Quorum Sensing During Infection.

Bacteria are highly interactive and possess an extraordinary repertoire of intercellular communication and social behaviors, including quorum sensing (QS). QS has been studied in detail at the molecular level, so mechanistic details are well understood in many species and are often involved in virulence. The use of different animal host models has demonstrated QS-dependent control of virulence determinants and virulence in several human pathogenic bacteria.

Combinatorial quorum sensing in allows for novel cheating strategies.

In the opportunistic pathogen quorum sensing (QS) is a social trait that is exploitable by non-cooperating cheats. Previously it has been shown that by linking QS to the production of both public and private goods, cheats can be prevented from invading populations of cooperators and this was described by Dandekar . (Science 2012;338:264-266) as 'a metabolic incentive to cooperate'.

Allelic polymorphism shapes community function in evolving Pseudomonas aeruginosa populations.

Pseudomonas aeruginosa is an opportunistic pathogen that chronically infects the lungs of individuals with cystic fibrosis (CF) by forming antibiotic-resistant biofilms. Emergence of phenotypically diverse isolates within CF P. aeruginosa populations has previously been reported; however, the impact of heterogeneity on social behaviors and community function is poorly understood.

Neoadjuvant Chemotherapy Shifts Breast Tumor Microbiota Populations to Regulate Drug Responsiveness and the Development of Metastasis.

Breast tumors have their own specific microbiota, distinct from normal mammary gland tissue. Patients with breast cancer that present with locally advanced disease often undergo neoadjuvant chemotherapy to reduce tumor size prior to surgery to allow breast conservation or limit axillary lymph node dissection. The purpose of our study was to evaluate whether neoadjuvant chemotherapy modulates the tumor microbiome and the potential impact of microbes on breast cancer signaling.

Microbe Profile: : opportunistic pathogen and lab rat.

is a Gram-negative opportunistic pathogen and a model bacterium for studying virulence and bacterial social traits. While it can be isolated in low numbers from a wide variety of environments including soil and water, it can readily be found in almost any human/animal-impacted environment. It is a major cause of illness and death in humans with immunosuppressive and chronic conditions, and infections in these patients are difficult to treat due to a number of antibiotic resistance mechanisms and the organism's propensity to form multicellular biofilms.

Competition in Biofilms between Cystic Fibrosis Isolates of Is Shaped by R-Pyocins.

is an opportunistic pathogen and the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. infections are difficult to treat due to a number of antibiotic resistance mechanisms and the organism's propensity to form multicellular biofilms. Epidemic strains of often dominate within the lungs of individual CF patients, but how they achieve this is poorly understood.

A simple mung bean infection model for studying the virulence of Pseudomonas aeruginosa.

Here we highlight the development of a simple and high-throughput mung bean model to study virulence in the opportunistic pathogen Pseudomonas aeruginosa. The model is easy to set up, and infection and virulence can be monitored for up to 10 days. In a first test of the model, we found that mung bean seedlings infected with PAO1 showed poor development of roots and high mortality rates compared to uninfected controls.

Corrigendum: Progress in and promise of bacterial quorum sensing research.

This corrects the article DOI: 10.1038/nature24624.

Progress in and promise of bacterial quorum sensing research.

This Review highlights how we can build upon the relatively new and rapidly developing field of research into bacterial quorum sensing (QS). We now have a depth of knowledge about how bacteria use QS signals to communicate with each other and to coordinate their activities. In recent years there have been extraordinary advances in our understanding of the genetics, genomics, biochemistry, and signal diversity of QS.