The classical bordetellae sense and respond to a variety of environments outside and within their mammalian hosts. By causing inflammation and tissue damage, we reasoned that bordetellae are likely to encounter components of blood and/or serum during the course of a respiratory infection, and that detecting and responding to these would be advantageous. Therefore, we hypothesized that classical bordetellae have the ability to sense and respond to blood or serum. Blood or serum exposure resulted in substantial transcriptional changes in Bordetella bronchiseptica, including enhanced expression of many virulence-associated genes. Exposure to blood or serum additionally elicited production of multiple antigens not otherwise detectable, and led to increased bacterial cytotoxicity against macrophages. Transcriptional responses to blood/serum were observed in a Bvg− phase-locked mutant, indicating that the response is not solely dependent on a functional BvgAS system. Similar transcriptional responses to blood/serum were observed for the other classical bordetellae, Bordetella pertussis and Bordetella parapertussis. These data suggest the classical bordetellae respond to signals present in blood and serum by changing their behavior in ways that likely contribute to their remarkable success, via effects on pathogenesis, persistence and/or transmission between hosts.

Communicable respiratory infections are the cause of a significant number of infectious diseases. The introduction of vaccinations has greatly improved this situation. Moreover, adjuvants have allowed for vaccines to be more effective with fewer adverse side effects. However, there is still space for improvement because while the more common injected formulations induce a systematic immunity, they do not confer the mucosal immunity needed for more thorough prevention of the spread of respiratory disease. Intranasal formulations provide systemic and mucosal immune protection, but they have the potential for more serious side effects and a less robust immune response. This review looks at seven different adjuvants—chitosan, starch, alginate, gellan, β-glucan, emulsan and hyaluronic acid—and their prospective ability to improve intranasal vaccines as adjuvants and antigen delivery systems.

Two-partner secretion (TPS) systems are broadly distributed among Gram-negative bacteria and play important roles in bacterial pathogenesis. FhaB-FhaC is the prototypical member of the TPS family and we here identified the protease that initiates a processing cascade that controls FhaB function.

Cystic fibrosis (CF) is one of the most prevalent genetic diseases and a total of 1700 different genetic mutations can cause this condition. Patients that suffer this disease have a thickening of the mucus, creating an environment that promotes bacterial infections. Pseudomonas aeruginosa is a ubiquitous bacterium, which is frequently found in the lungs of CF patients. P. aeruginosa is known for its high level of antibiotic resistance as well as its high rate of mutation that allows it to rapidly evolve and adapt to a multitude of conditions. When a CF lung is infected with P. aeruginosa, the decay of the patient is accelerated, but there is little that can be done apart from controlling the infection with antibiotics. Novel strategies to control P. aeruginosa infection are imperative, and nanotechnology provides novel approaches to drug delivery that are more efficient than classic antibiotic treatments. These drug delivery systems are offering new prospects, especially for these patients with special mucus conditions and bacterial characteristics that limit antibiotic use.

Infectious diseases are the primary cause of mortality worldwide. The dangers of infectious disease are compounded with antimicrobial resistance, which remains the greatest concern for human health. Although novel approaches are under investigation, the World Health Organization predicts that by 2050, septicaemia caused by antimicrobial resistant bacteria could result in 10 million deaths per year. One of the main challenges in medical microbiology is to develop novel experimental approaches, which enable a better understanding of bacterial infections and antimicrobial resistance. After the introduction of whole genome sequencing, there was a great improvement in bacterial detection and identification, which also enabled the characterization of virulence factors and antimicrobial resistance genes. Today, the use of in silico experiments jointly with computational and machine learning offer an in depth understanding of systems biology, allowing us to use this knowledge for the prevention, prediction, and control of infectious disease. Herein, the aim of this review is to discuss the latest advances in human health engineering and their applicability in the control of infectious diseases. An in-depth knowledge of host–pathogen–protein interactions, combined with a better understanding of a host’s immune response and bacterial fitness, are key determinants for halting infectious diseases and antimicrobial resistance dissemination.

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Filamentous hemagglutinin (FhaB) is a critical virulence factor for both Bordetella bronchiseptica, the causal agent of whooping cough, and the closely related species Bordetella bronchiseptica. FhaB is an adhesin, suppresses inflammatory cytokine production, and protects against phagocytic cell clearance during infection. Regulated degradation of the FhaB C-terminal prodomain is required to establish a persistent infection in mice. Two proteases, CtpA in the periplasm and SphB1 on the bacterial surface, mediate FhaB processing, and we recently determined that CtpA functions before, and controls the FhaB cleavage site of, SphB1. However, the data indicate that another periplasmic protease must initiate degradation of the prodomain by removing a portion of the FhaB C terminus that inhibits CtpA-mediated degradation. Using a candidate approach, we identified DegP as the initiating protease. Deletion of degP or substitution of its predicted catalytic residue resulted in reduced creation of FHA', the main product of FhaB processing, and an accumulation of full-length FhaB in whole cell lysates. Also, FHA' was no longer released into culture supernatants in degP mutants. Alterations of the FhaB C terminus that relieve inhibition of CtpA abrogate the need for DegP, consistent with DegP functioning prior to CtpA in the processing pathway. DegP is not required for secretion of FhaB through FhaC or for adherence of the bacteria to host cells, indicating that DegP acts primarily as a protease and not a chaperone for FhaB in B. bronchiseptica. Our results highlight a role for HtrA family proteases in activation of virulence factors in pathogenic bacteria.