Effect of respiratory tract co-colonizers on initial attachment of Neisseria meningitidis.

Respiratory tract is a complex system comprising of unique microbiota inhabitants. Neisseria meningitidis, Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa and Klebsiella pneumoniae are few prevalent bacteria in the community composition during lung infections. Although, N. meningitidis resides asymptomatically in nasopharynx of the human host, it can cause fatal infections like meningitis. However, factors affecting transit from carriage to symptomatic infection are not well understood. Various host metabolites and environmental conditions affect the virulence of bacteria. Here, we report that presence of co-colonizers significantly reduces the initial attachment of N. meningitidis to A549 nasopharyngeal epithelial cells. Further, significant decrease in invasion to A549 nasopharyngeal epithelial cells was observed. Moreover, survival in J774A.1 murine macrophage also increases significantly when conditioned media (CM) from S. pyogenes and L. rhamnosus is used for culturing N. meningitidis. The increase in survival could be attributed to increased capsule synthesis. The gene expression studies revealed increased expression of siaC and ctrB in CM prepared from the growth S. pyogenes and L. rhamnosus. Overall, the results suggest change in the virulence of N. meningitidis is assisted by lung microbiota.

The source of carbon and nitrogen differentially affects the survival of Neisseria meningitidis in macrophages and epithelial cells.

Neisseria meningitidis is a commensal of human nasopharynx which under certain unidentified conditions could lead to fulminant meningitis or sepsis. Availability of nutrients is essential for bacterial growth and virulence. The metabolic adaptations allow N. meningitidis to utilize host resources, colonize and cause virulence functions which are a crucial for the invasive infection. During colonization meningococci encounters a range of microenvironments involving fluctuations in the availability of carbon and nitrogen source. Therefore, the characterization of virulence factors of N. meningitidis under different microenvironmental conditions is a prime requisite to understand pathogenesis; however, the role of nutrients is not well understood. Here, we explore the expression of virulence phenotype leading to symptomatic behaviour as affected by available carbon and nitrogen sources. We evaluate the effect of carbon or nitrogen source on growth, adhesion to epithelial cells, macrophage infectivity, capsule formation and virulence gene expression of N. meningitidis. It was found that lactate, pyruvate, and acetate facilitate survival of N. meningitidis in macrophages. While in epithelial cells, the survival of N. meningitidis is negatively affected by the presence of lactate and pyruvate.

Availability of polyamines affects virulence and survival of Neisseria meningitidis.

Neisseria meningitidis is a Gram-negative human-restricted pathogen that asymptomatically resides in the human respiratory tract. Meningococcal meningitis and sepsis both are caused by N. meningitidis. The bacterium must adhere to host epithelial cells in order to colonize effectively. The factors that determine the initial attachment to the host and dispersal, are not well understood. Metabolites released by the host may aid in meningococcal colonization and dissemination. Polyamines are aliphatic polycations that assist in cell survival and proliferation. The virulence properties of N. meningitidis after exposure to polyamines were investigated. Adhesion to nasopharyngeal epithelial cells increased in the presence of spermine. Also, the relative expression of adhesin, pilE increased in the presence of spermine. Further, relative expression of ctrA, ctrB and lipB was upregulated in the presence of spermidine, indicating increased capsule formation. Upregulated capsule synthesis of N. meningitidis in the presence of spermidine allows it to survive in murine macrophages. The study suggests the importance of the extracellular pool of polyamines in promoting virulence in N. meningitidis.

Foodborne ESKAPE Biofilms and Antimicrobial Resistance: lessons Learned from Clinical Isolates.

The ESKAPE pathogens (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) are identified to be multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan drug-resistant (PDR); thereby, imposing severe challenges in the treatment of associated infections. ESKAPE pathogens colonize on various biotic and abiotic surfaces; biofilms formed by these pathogens are a potential source for food contamination. Moreover, biofilms play a pivotal role in the development of antimicrobial-resistant (AMR) strains. Hence, the frequent isolation of antimicrobial-resistant ESKAPE pathogens from food products across the globe imposes a threat to public health. A comprehensive understanding of the adhesion signaling involved in the polymicrobial and single-species biofilm will assist in developing alternative preservation techniques and novel therapeutic strategies to combat ESKAPE pathogens. The review provides a comprehensive overview of the signaling mechanisms that prevail in the ESKAPE pathogens for adhesion to abiotic and biotic surfaces and molecular mechanisms associated with poly-microbial biofilm-assisted AMR in ESKAPE.

Pore-forming toxins of foodborne pathogens.

Pore-forming toxins (PFTs) are water-soluble molecules that have been identified as the most crucial virulence factors during bacterial pathogenesis. PFTs disrupt the host cell membrane to internalize or to deliver other bacterial or virulence factors for establishing infections. Disruption of the host cell membrane by PFTs can lead to uncontrollable exchanges between the extracellular and the intracellular matrix, thereby disturbing the cellular homeostasis. Recent studies have provided insights into the molecular mechanism of PFTs during pathogenesis. Evidence also suggests the activation of several signal transduction pathways in the host cell on recognition of PFTs. Additionally, numerous distinctive host defense mechanisms as well as membrane repair mechanisms have been reported; however, studies reveal that PFTs aid in host immune evasion of the bacteria through numerous pathways. PFTs have been primarily associated with foodborne pathogens. Infection and death from diseases by consuming contaminated food are a constant threat to public health worldwide, affecting socioeconomic development. Moreover, the emergence of new foodborne pathogens has led to the rise of bacterial antimicrobial resistance affecting the population. Hence, this review focuses on the role of PFTs secreted by foodborne pathogens. The review highlights the molecular mechanism of foodborne bacterial PFTs, assisting bacterial survival from the host immune responses and understanding the downstream mechanism in the activation of various signaling pathways in the host upon PFT recognition. PFT research is a remarkable and an important field for exploring novel and broad applications of antimicrobial compounds as therapeutics.

Bacteriophages for ESKAPE: role in pathogenicity and measures of control.

INTRODUCTION: The quest to combat bacterial infections has dreaded humankind for centuries. Infections involving ESKAPE (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) impose therapeutic challenges due to the emergence of antimicrobial drug resistance. Recently, investigations with bacteriophages have led to the development of novel strategies against ESKAPE infections. Also, bacteriophages have been demonstrated to be instrumental in the dissemination of virulence markers in ESKAPE pathogens. AREAS COVERED: The review highlights the potential of bacteriophage in and against the pathogenicity of antibiotic-resistant ESKAPE pathogens. The review also emphasizes the challenges of employing bacteriophage in treating ESKAPE pathogens and the knowledge gap in the bacteriophage mediated antibiotic resistance and pathogenicity in ESKAPE infections. EXPERT OPINION: Bacteriophage infection can kill the host bacteria but in survivors can transfer genes that contribute toward the survival of the pathogens in the host and resistance toward multiple antimicrobials. The knowledge on the dual role of bacteriophages in the treatment and pathogenicity will assist in the prediction and development of novel therapeutics targeting antimicrobial-resistant ESKAPE. Therefore, extensive investigations on the efficacy of synthetic bacteriophage, bacteriophage cocktails, and bacteriophage in combination with antibiotics are needed to develop effective therapeutics against ESKAPE infections.

Polyamines in the virulence of bacterial pathogens of respiratory tract.

Polyamines are positively charged hydrocarbons that are essential for the growth and cellular maintenance in prokaryotes and eukaryotes. Polyamines have been demonstrated to play a role in bacterial pathogenicity and biofilm formation. However, the role of extracellular polyamines as a signaling molecule in the regulation of virulence is not investigated in detail. The bacterial pathogens residing in the respiratory tract remain asymptomatic for an extended period; however, the factors that lead to symptomatic behavior are poorly understood. Further investigation to understand the relation between the host-secreted factors and virulence of pathogenic bacteria in the respiratory tract may provide insights into the pathogenesis of respiratory tract infections. Polyamines produced within the bacterial cell are generally sequestered. Therefore, the pool of extracellular polyamines formed by secretion of the commensals and the host may be one of the signaling molecules that might contribute toward the alterations in the expression of virulence factors in bacterial pathogens. Besides, convergent mechanisms of polyamine biosynthesis do exist across the border of species and genus level. Also, several novel polyamine transporters in the host and bacteria remain yet to be identified. The review focuses on the role of polyamines in the expression of virulence phenotypes and biofilm formation of the respiratory tract pathogens.

Role of interspecies bacterial communication in the virulence of pathogenic bacteria.

Bacteria live in a polymicrobial community where it interacts with biotic and abiotic factors using specific signalling molecules. Acyl homoserine lactones, autoinducing peptides, bacteriocins and polyamines are a few signals documented for interspecies signalling. The signalling system could be used for a coordinated behaviour categorised as Quorum sensing (QS). QS is a term used to define a cell - cell communication process amongst bacteria that helps to gather cell density information and regulate gene expression accordingly. QS had been demonstrated to play a pivotal role in bacterial pathogenesis by regulating the expression of different virulence factors affecting adhesion, invasion and survival within a tissue. In the current review, we discuss the role of interspecies bacterial communication in pathogenicity. The molecules involved in the interspecies bacterial communication affecting virulence factors required for the establishment of infection have been discussed in detail to gain an insight for development of strategies that can be proposed to combat bacterial infections by attenuating their communication systems. The knowledge on the role of interspecies bacterial communication on virulence will assist in understanding the factors affecting symptomatic and asymptomatic infections.