PMID- 23163337 OWN - NLM STAT- MEDLINE DCOM- 20130702 LR - 20191210 IS - 1365-2958 (Electronic) IS - 0950-382X (Linking) VI - 87 IP - 1 DP - 2013 Jan TI - Genetic requirements for Moraxella catarrhalis growth under iron-limiting conditions. PG - 14-29 LID - 10.1111/mmi.12081 [doi] AB - Iron sequestration by the human host is a first line defence against respiratory pathogens like Moraxella catarrhalis, which consequently experiences a period of iron starvation during colonization. We determined the genetic requirements for M. catarrhalis BBH18 growth during iron starvation using the high-throughput genome-wide screening technology genomic array footprinting (GAF). By subjecting a large random transposon mutant library to growth under iron-limiting conditions, mutants of the MCR_0996-rhlB-yggW operon, rnd, and MCR_0457 were negatively selected. Growth experiments using directed mutants confirmed the GAF phenotypes with DeltayggW (putative haem-shuttling protein) and DeltaMCR_0457 (hypothetical protein) most severely attenuated during iron starvation, phenotypes which were restored upon genetic complementation of the deleted genes. Deletion of yggW resulted in similar attenuated phenotypes in three additional strains. Transcriptional profiles of DeltayggW and DeltaMCR_0457 were highly altered with 393 and 192 differentially expressed genes respectively. In all five mutants, expression of nitrate reductase genes was increased and of nitrite reductase decreased, suggesting an impaired aerobic respiration. Alteration of iron metabolism may affect nasopharyngeal colonization as adherence of all mutants to respiratory tract epithelial cells was attenuated. In conclusion, we elucidated the genetic requirements for M. catarrhalis growth during iron starvation and characterized the roles of the identified genes in bacterial growth and host interaction. CI - (c) 2012 Blackwell Publishing Ltd. FAU - de Vries, Stefan P W AU - de Vries SP AD - Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, Nijmegen, the Netherlands. FAU - Burghout, Peter AU - Burghout P FAU - Langereis, Jeroen D AU - Langereis JD FAU - Zomer, Aldert AU - Zomer A FAU - Hermans, Peter W M AU - Hermans PW FAU - Bootsma, Hester J AU - Bootsma HJ LA - eng SI - GEO/GSE41546 SI - GEO/GSE41547 SI - GEO/GSE41548 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121119 PL - England TA - Mol Microbiol JT - Molecular microbiology JID - 8712028 RN - E1UOL152H7 (Iron) SB - IM MH - Gene Deletion MH - Gene Expression Profiling MH - Humans MH - Iron/*metabolism MH - Microarray Analysis MH - Moraxella catarrhalis/genetics/*growth & development/*metabolism MH - Phenotype MH - Signal Transduction EDAT- 2012/11/21 06:00 MHDA- 2013/07/03 06:00 CRDT- 2012/11/21 06:00 PHST- 2012/10/20 00:00 [accepted] PHST- 2012/11/21 06:00 [entrez] PHST- 2012/11/21 06:00 [pubmed] PHST- 2013/07/03 06:00 [medline] AID - 10.1111/mmi.12081 [doi] PST - ppublish SO - Mol Microbiol. 2013 Jan;87(1):14-29. doi: 10.1111/mmi.12081. Epub 2012 Nov 19.