How Can Antimicrobial Resistance in Pseudomonas aeruginosa Be Controlled?

Pseudomonas aeruginosa remains one of the most difficult to treat and to control nosocomial infections. In vitro antimicrobial susceptibility data are required for successful therapy because acquired resistance to such antimicrobials as β-lactams, fluoroquinolones and aminoglycosides is so prevalent in P. aeruginosa. Strategies for controlling P. aeruginosa infections include early detection of P. aeruginosa as the causative pathogen, determination of its antimicrobial susceptibilities, initiation of effective and adequate therapy and strict infection control practice such as hand hygiene and equipment procedures. Once antimicrobial therapy has been initiated against a P. aeruginosa infection, its susceptibility to antimicrobials, especially to carbapenems and fluoroquinolones, should be monitored during antimicrobial therapy to detect clonal shifts in resistance and microbial substitutions as early as possible. Continued surveillance of nosocomial infections and monitoring of antimicrobial resistance by the infection control staff plays major roles in preventing nosocomial infections and the spread of antimicrobial resistance. Additional strategies for controlling antimicrobial resistance in P. aeruginosa include the development of new methods for rapid detection of antimicrobial resistance and new agents and vaccines against P. aeruginosa infections in the laboratories and pharmaceuticals, while preserving the efficacy of currently available antimicrobials for as long as possible in the hospital settings

Autophagy adaptor protein p62/SQSTM1 and autophagy-related gene Atg5 mediate autophagosome formation in response to Mycobacterium tuberculosis infection in dendritic cells.

Mycobacterium tuberculosis is an intracellular pathogen that can survive within phagocytic cells by inhibiting phagolysosome biogenesis. However, host cells can control the intracellular M. tuberculosis burden by the induction of autophagy. The mechanism of autophagosome formation to M. tuberculosis has been well studied in macrophages, but remains unclear in dendritic cells. We therefore characterized autophagosome formation in response to M. tuberculosis infection in dendritic cells. Autophagy marker protein LC3, autophagy adaptor protein p62/SQSTM1 (p62) and ubiquitin co-localized to M. tuberculosis in dendritic cells. Mycobacterial autophagosomes fused with lysosomes during infection, and major histcompatibility complex class II molecules (MHC II) also localized to mycobacterial autophagosomes. The proteins p62 and Atg5 function in the initiation and progression of autophagosome formation to M. tuberculosis, respectively; p62 mediates ubiquitination of M. tuberculosis and Atg5 is involved in the trafficking of degradative vesicles and MHC II to mycobacterial autophagosomes. These results imply that the autophagosome formation to M. tuberculosis in dendritic cells promotes the antigen presentation of mycobacterial peptides to CD4(+) T lymphocytes via MHC II

Bacillus cereus Bloodstream Infection in a Preterm Neonate Complicated by Late Meningitis

Central nervous system infections caused by Bacillus cereus have rarely been reported in infants. In this paper, the case of a 2-month-old low-birth-weight female who developed meningitis 45 days after resolution of a bloodstream infection (BSI) is described. The pulsed-field gel electrophoresis results revealed that the patterns of both B. cereus isolates responsible for the acute meningitis and for the prior bacteraemic episode were closely related. Although the source of the infection from within the patient was not clear, it is suggested that the B. cereus BSI developed in the neonate was complicated by acute meningitis

Atg5-dependent localization of LAMP1 and MHC class II to mycobacterial autophagosomes.

<p>(A-C) Thin-section electron micrograph of <i>M. tuberculosis</i> bacilli in p62- or Atg5-knockdown DC. DC2.4 cells transfected with siRNA for control (A), p62 (B) or Atg5 (C) were infected with <i>M. tuberculosis</i> for 24 h and observed by thin-section electron microscopy. Autophagosomes are indicated by arrowheads. (D) Proportion of mycobacteria in multi-membrane structures in DC2.4 transfected with siRNA for p62 or Atg5. (E, F) The proportion of LAMP1 (E) or MHC class II (F) localization to ubiquitin-positive mycobacteria is shown. JAWSII cells transfected with control or Atg5 siRNA for 24 h were infected with Alexa Fluor 405-labeled <i>M. tuberculosis</i> and immunostained with anti-LAMP1 and anti-ubiquitin antibodies or anti-MHC class II and anti-ubiquitin antibodies. Data represent the mean and SD of three independent experiments. *<i>p</i> < 0.05 (unpaired Student’s <i>t</i>-test).</p

Maturation of mycobacterial autophagosomes in DC2.4 cells.

<div><p>(A) Recruitment of p62 to LC3-positive mycobacteria. DC2.4 cells were infected with Alexa Fluor 405-labeled <i>M. tuberculosis</i> (blue) for 24 h and immunostained with anti-LC3 (green) and anti-p62 antibodies (red). (B) The proportion of p62 localization to LC3-positive mycobacteria in DC2.4 cells. </p> <p>(C) Recruitment of ubiquitin to p62-positive mycobacteria. DC2.4 cells were infected with Alexa Fluor 405-labeled <i>M. tuberculosis</i> (blue) for 24 h and immunostained with anti-p62 (red) and anti-ubiquitin antibodies (green). (D) The proportion of ubiquitin localization to p62-positive mycobacteria in DC2.4 cells. Data represent the mean and SD of three independent experiments.</p></div

p62-dependent ubiquitination of mycobacteria in DC.

<p>(A) The proportion of LC3, p62 or ubiquitin recruitment to mycobacteria in DC treated with 3-MA. DC2.4 were infected with DsRed-expressing <i>M. tuberculosis</i> for 24 h with or without 3-MA and immunostained with anti-LC3, anti-p62 or anti-ubiquitin antibodies. Data represent the mean and SD of three or four independent experiments. *<i>p</i> < 0.05 (unpaired Student’s <i>t</i>-test). (B) Immunoblot analysis on the silencing effects of p62 and Atg5. DC2.4 cells were transfected with siRNA for p62 or Atg5 for 48 h and subjected to immunoblot analysis using indicated antibodies. (C, D) The proportion of p62 or ubiquitin recruitment to mycobacteria in DC. DC2.4 cells transfected with siRNA for p62 or Atg5 were infected with DsRed-expressing <i>M. tuberculosis</i> for 12 h and immunostained with anti-p62 (C) or anti-ubiquitin (D) antibody. Data represent the mean and SD of three independent experiments. *<i>p</i> < 0.05 (unpaired Student’s <i>t</i>-test).</p