Inhibition of macrophage infectivity potentiator in suppresses pro-inflammatory responses in murine macrophages.

Introduction: Melioidosis, caused by the Gram-negative bacterium , is a disease endemic in many tropical countries globally. Clinical presentation is highly variable, ranging from asymptomatic to fatal septicemia, and thus the outcome of infection can depend on the host immune responses. The aims of this study were to firstly, characterize the macrophage immune response to and secondly, to determine whether the immune response was modified in the presence of novel inhibitors targeting the virulence factor, the macrophage infectivity potentiator (Mip) protein.

Pathogenicity and virulence of .

The soil saprophyte, , is the causative agent of melioidosis, a disease endemic in South East Asia and northern Australia. Exposure to by either inhalation or inoculation can lead to severe disease. rapidly shifts from an environmental organism to an aggressive intracellular pathogen capable of rapidly spreading around the body.

Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major.

Background: The macrophage infectivity potentiator (Mip) protein, which belongs to the immunophilin superfamily, is a peptidyl-prolyl cis/trans isomerase (PPIase) enzyme. Mip has been shown to be important for virulence in a wide range of pathogenic microorganisms. It has previously been demonstrated that small-molecule compounds designed to target Mip from the Gram-negative bacterium Burkholderia pseudomallei bind at the site of enzymatic activity of the protein, inhibiting the in vitro activity of Mip.

Targeting Protein Folding: A Novel Approach for the Treatment of Pathogenic Bacteria.

Infectious diseases are a major cause of morbidity and mortality worldwide, exacerbated by increasing antibiotic resistance in many bacterial species. The development of drugs with new modes of action is essential. A leading strategy is antivirulence, with the aim to target bacterial proteins that are important in disease causation and progression but do not affect growth, resulting in reduced selective pressure for resistance.

Peptidyl-Prolyl Isomerase Is Essential for Proteome Homeostasis and Virulence in Burkholderia pseudomallei.

is the causative agent of melioidosis, a disease endemic to Southeast Asia and northern Australia. Mortality rates in these areas are high even with antimicrobial treatment, and there are few options for effective therapy. Therefore, there is a need to identify antibacterial targets for the development of novel treatments.

Field trials of blood culture identification FilmArray in regional Australian hospitals.

In this field trial of rapid blood culture identification (BCID), we aimed to determine whether the improved speed and accuracy of specific BCID predicted in our earlier pilot study could be obtained in regional hospitals by deploying a multiplex PCR FilmArray (Biomerieux, France) capability in their laboratories. We trained local hospital laboratory staff to operate the FilmArray equipment and act on the results. To do this, we integrated the multiplex PCR into the standard laboratory blood culture workflow and reporting procedure.

Inhibitors of macrophage infectivity potentiator-like PPIases affect neisserial and chlamydial pathogenicity.

The pathogenic bacteria Chlamydia trachomatis, Neisseria gonorrhoeae and Neisseria meningitidis express the surface-exposed macrophage infectivity potentiator (MIP)-like protein, which plays a role in their pathogenicity. MIP exhibits a peptidyl-prolyl isomerase (PPIase) activity that is inhibited by rapamycin and FK506. In this study, pipecolic acid derivatives were tested for their activity against the chlamydial and neisserial MIP.

Improved blood culture identification by FilmArray in cultures from regional hospitals compared with teaching hospital cultures.

Rapid identification of bacteria isolated from blood cultures by direct matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is now in wide spread use in major centres but is not yet feasible in smaller hospital laboratories. A FilmArray multiplex PCR panel for blood culture isolate identification (BCID) provides an alternative approach to near point-of-care microbial identification in regional hospitals. We assessed the accuracy and time to identification of the BCID FilmArray in a consecutive series of 149 blood cultures from 143 patients in a teaching hospital and smaller regional hospitals, currently identified by direct MALDI-TOF and proprietary molecular methods.