title: Regulation of expression of abcA and its response to environmental conditions.
abstract: The ATP-dependent transporter gene abcA in Staphylococcus aureus confers resistance to hydrophobic β-lactams. In strain ISP794, abcA is regulated by the transcriptional regulators MgrA and NorG and shares a 420-nucleotide intercistronic region with the divergently transcribed pbp4 gene, which encodes the transpeptidase Pbp4. Exposure of exponentially growing cells to iron-limited media, oxidative stress, and acidic pH (5.5) for 0.5 to 2 h had no effect on abcA expression. In contrast, nutrient limitation produced a significant increase in abcA transcripts. We identified three additional regulators (SarA, SarZ, and Rot) that bind to the overlapping promoter region of abcA and pbp4 in strain MW2 and investigated their role in the regulation of abcA expression. Expression of abcA is decreased by 10.0-fold in vivo in a subcutaneous abscess model. In vitro, abcA expression depends on rot and sarZ regulators. Moenomycin A exposure of strain MW2 produced an increase in abcA transcripts. Relative to MW2, the MIC of moenomycin was decreased 8-fold for MW2ΔabcA and increased 10-fold for the MW2 abcA overexpresser, suggesting that moenomycin is a substrate of AbcA.
authors: Division of Infectious Diseases and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Regis A
authors: RA
authors: Villet
authors: Que Chi
authors: QC
authors: Truong-Bolduc
authors: Yin
authors: Y
authors: Wang
authors: Zoe
authors: Z
authors: Estabrooks
authors: Heidi
authors: H
authors: Medeiros
authors: David C
authors: DC
authors: Hooper
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000038:Abscess / Q000382:microbiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001455:Bambermycins / Q000378:metabolism; D001483:Base Sequence; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D013207:Staphylococcal Skin Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013312:Stress, Physiological; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012097:Repressor Proteins; C088021:SarA protein, bacterial; C534537:SarZ protein, Staphylococcus aureus; D015534:Trans-Activators; D014157:Transcription Factors; C408643:rot protein, Staphylococcus aureus; D001455:Bambermycins; C437243:moenomycin A; D007501:Iron