ABSTRACT
Pneumocystis pneumonia is an important human immunodeficiency virus (HIV)-associated opportunistic infection, and especially so in pregnant HIV-positive patients. We report a case of a 40-year-old woman in her first trimester of pregnancy who initially presented with acute gastroenteritis symptoms but due to a history of high-risk behaviour and the observation of oral thrush, she was worked up for HIV infection. Her retroviral status was positive and her CD4+ T cell count was only 8 cells/mL. She was also worked up for pneumocystis pneumonia due to the presence of mild resting tachypnoea and a notable drop in oxygen saturation (from 100% to 88%) following brief ambulation. Her chest radiograph revealed bilaterally symmetrical lower zone reticular opacities and Giemsa staining of her bronchoalveolar lavage (BAL) was negative for Pneumocystis jirovecii cysts. However, real-time P. jirovecii polymerase chain reaction (PCR) testing on the same BAL specimen revealed the presence of the organism. A course of oral co-trimoxazole plus prednisolone was commenced and her clinical condition improved.
ABSTRACT
Aims: VraSR and GraSR were shown to be important in conferring intermediate vancomycin resistance in VISA. Nevertheless, the exact mechanism modulated by these systems leading to the development of VISA remains unclear. We employed a proteomic approach to determine the VraS and GraR regulons and subsequently derive the possible vancomycin resistance regulatory pathway(s) in the Mu50 lineage of Staphylococcus aureus. Methodology and results: Staphylococcus aureus strains Mu50Ω, Mu50Ω-vraSm and Mu50Ω-vraSm-graRm are isogenic strains with ascending levels of vancomycin resistance. Total proteins were extracted from the 3 strains and trypsin digested prior to protein isolation and identification by LC-ESI MS/MS and PLGS 2.4. Expression profiles of resulting proteins were analyzed using Progenesis LC/MS software. Differential expression profiles revealed 3 regulons, each controlled by VraS (Mu50Ω-vraSm vs Mu50Ω), GraR (Mu50Ω-vraSm-graRm vs Mu50Ω-vraSm) and VraS-GraR (Mu50Ω-vraSm-graRm vs Mu50Ω), respectively. The regulon down-regulated by VraS in Mu50Ω-vraSm were proteins associated with virulence (MgrA, Rot, and SarA), while GraR up-regulated resistance-associated proteins (TpiA, ArcB and IsaA) in Mu50Ω-vraSm-graRm. The VraS-GraR regulon mediated both up-regulation of resistance-associated proteins (ArgF, ArcB, VraR and SerS) and down-regulation of virulence-associated protein GapB. Conclusion, significance and impact of study: Down-regulation of virulence- in concert with up-regulation of resistance-associated proteins appears to be integral for development of intermediate-vancomycin resistance in the Mu50 lineage of S. aureus.