Transcriptional Profiling of Coxiella burnetii Reveals Extensive Cell Wall Remodeling in the Small Cell Variant Developmental Form

Sandoz, Kelsi M.; Popham, David L.; Beare, Paul A.; Sturdevant, Daniel E.; Hansen, Bryan; Nair, Vinod; Heinzen, Robert A.

doi:10.1371/journal.pone.0149957

Cited by 54 publications

(76 citation statements)

References 120 publications

(154 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Structural rigidity in SCV-form Coxiella is partially conferred by a thick peptidoglycan, and it has recently been shown that this is characterised by an abundance of LD-transpeptidase-mediated 3-3 peptide cross-links (Sandoz et al, 2016).…”

Section: Coxiella Burnettiimentioning

confidence: 99%

Peptidoglycan in obligate intracellular bacteria

Otten

Brilli

Vollmer

et al. 2017

Molecular Microbiology

View full text Add to dashboard Cite

SummaryPeptidoglycan is the predominant stress‐bearing structure in the cell envelope of most bacteria, and also a potent stimulator of the eukaryotic immune system. Obligate intracellular bacteria replicate exclusively within the interior of living cells, an osmotically protected niche. Under these conditions peptidoglycan is not necessarily needed to maintain the integrity of the bacterial cell. Moreover, the presence of peptidoglycan puts bacteria at risk of detection and destruction by host peptidoglycan recognition factors and downstream effectors. This has resulted in a selective pressure and opportunity to reduce the levels of peptidoglycan. In this review we have analysed the occurrence of genes involved in peptidoglycan metabolism across the major obligate intracellular bacterial species. From this comparative analysis, we have identified a group of predicted ‘peptidoglycan‐intermediate’ organisms that includes the Chlamydiae, Orientia tsutsugamushi, Wolbachia and Anaplasma marginale. This grouping is likely to reflect biological differences in their infection cycle compared with peptidoglycan‐negative obligate intracellular bacteria such as Ehrlichia and Anaplasma phagocytophilum, as well as obligate intracellular bacteria with classical peptidoglycan such as Coxiella, Buchnera and members of the Rickettsia genus. The signature gene set of the peptidoglycan‐intermediate group reveals insights into minimal enzymatic requirements for building a peptidoglycan‐like sacculus and/or division septum.

show abstract

Section: Coxiella Burnettiimentioning

confidence: 99%

Peptidoglycan in obligate intracellular bacteria

Otten

Brilli

Vollmer

et al. 2017

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

“…Genes associated with SCV differentiation are regulated by RpoS. The large cohort of RpoS-regulated genes directed us to focus on four subsets of genes that were previously shown to be developmentally regulated during SCV differentiation (25). Thirty-two SCV-associated genes were related to arginine transport/metabolism, cell wall remodeling, and responses to general and oxidative stress.…”

Section: Resultsmentioning

confidence: 99%

Coxiella burnetii RpoS Regulates Genes Involved in Morphological Differentiation and Intracellular Growth

et al. 2019

Self Cite

View full text Add to dashboard Cite

Coxiella burnetii, the etiological agent of Q fever, undergoes a unique biphasic developmental cycle where bacteria transition from a replicating (exponentialphase) large cell variant (LCV) form to a nonreplicating (stationary-phase) small cell variant (SCV) form. The alternative sigma factor RpoS is an essential regulator of stress responses and stationary-phase physiology in several bacterial species, including Legionella pneumophila, which has a developmental cycle superficially similar to that of C. burnetii. Here, we used a C. burnetii ΔrpoS mutant to define the role of RpoS in intracellular growth and SCV development. Growth yields following infection of Vero epithelial cells or THP-1 macrophage-like cells with the rpoS mutant in the SCV form, but not the LCV form, were significantly lower than that of wild-type bacteria. RNA sequencing and whole-cell mass spectrometry of the C. burnetii ΔrpoS mutant revealed that a substantial portion of the C. burnetii genome is regulated by RpoS during SCV development. Regulated genes include those involved in stress responses, arginine transport, peptidoglycan remodeling, and synthesis of the SCVspecific protein ScvA. Genes comprising the dot/icm locus, responsible for production of the Dot/Icm type 4B secretion system, were also dysregulated in the rpoS mutant. These data were corroborated with independent assays demonstrating that the C. burnetii ΔrpoS strain has increased sensitivity to hydrogen peroxide and carbenicillin and a thinner cell wall/outer membrane complex. Collectively, these results demonstrate that RpoS is an important regulator of genes involved in C. burnetii SCV development and intracellular growth. IMPORTANCE The Q fever bacterium Coxiella burnetii has spore-like environmental stability, a characteristic that contributes to its designation as a potential bioweapon. Stability is likely conferred by a highly resistant, small cell variant (SCV) stationaryphase form that arises during a biphasic developmental cycle. Here, we define the role of the alternative sigma factor RpoS in regulating genes associated with SCV development. Genes involved in stress responses, amino acid transport, cell wall remodeling, and type 4B effector secretion were dysregulated in the rpoS mutant. Cellular impairments included defects in intracellular growth, cell wall structure, and resistance to oxidants. These results support RpoS as a central regulator of the Coxiella developmental cycle and identify developmentally regulated genes involved in morphological differentiation.

show abstract

“…Furthermore, unless PG is purified from intracellular bacteria, it is not possible to definitively conclude the selective pressure that the host has imposed on intracellular pathogens. As my group and a few others have shown (Mahapatra et al, ; Packiam et al, ; Pilhofer et al, ; Quintela et al, ; Sandoz et al, ), it is possible to isolate PG directly from the infected cells and this information is crucial to understand these host‐pathogen interactions. Another fascinating fact is the presence of PG containing D‐amino acids in moss chloroplasts (Hirano et al, ).…”

Section: Future Directionsmentioning

confidence: 96%

“…This, therefore, continues to be the major obstacle when attempting to purify PG from a reduced number of bacteria, as it is the case in most in vitro and in vivo infection models with intracellular bacterial pathogens and endosymbionts. The few successful cases of muropeptide characterization include those of the obligate bacterial pathogens Chlamydia trachomatis (Packiam, Weinrick, Jacobs, & Maurelli, 2015), Coxiella burnetii (Sandoz et al, 2016), and Mycobacterium leprae (Mahapatra, Crick, McNeil, & Brennan, 2008); the facultative intracellular pathogen Salmonella enterica serovar Typhimurium (Quintela, Pedro, Zollner, Allmaier, & Garcia-del Portillo, 1997); and the Acanthamoeba spp. endosymbiont Protochlamydia amoebophila (Pilhofer et al, 2013).…”

Section: An P G S Truc Ture and Enz Ymology B E Monitored In Intrmentioning

confidence: 99%

“…As my group and a few others have shown (Mahapatra et al, 2008;Packiam et al, 2015;Pilhofer et al, 2013;Quintela et al, 1997;Sandoz et al, 2016), it is possible to isolate PG directly from the infected cells and this information is crucial to understand these host-pathogen interactions. Another fascinating fact is the presence of PG containing D-amino acids in moss chloroplasts (Hirano et al, 2016).…”

Section: Future D Irec Ti On Smentioning

confidence: 99%

See 1 more Smart Citation

Building peptidoglycan inside eukaryotic cells: A view from symbiotic and pathogenic bacteria

Portillo

2020

Molecular Microbiology

View full text Add to dashboard Cite

The peptidoglycan (PG), as the exoskeleton of most prokaryotes, maintains a defined shape and ensures cell integrity against the high internal turgor pressure. These important roles have attracted researchers to target PG metabolism in order to control bacterial infections. Most studies, however, have been performed in bacteria grown under laboratory conditions, leading to only a partial view on how the PG is synthetized in natural environments. As a case in point, PG metabolism and its regulation remain poorly understood in symbiotic and pathogenic bacteria living inside eukaryotic cells. This review focuses on the PG metabolism of intracellular bacteria, emphasizing the necessity of more in vivo studies involving the analysis of enzymes produced in the intracellular niche and the isolation of PG from bacteria residing within eukaryotic cells. The review also points to persistent infections caused by some intracellular bacterial pathogens and the extent at which the PG could contribute to establish such physiological state. Based on recent evidences, I speculate on the idea that certain structural features of the PG may facilitate attenuation of intracellular growth. Lastly, I discuss recent findings in endosymbionts supporting a cooperation between host and bacterial enzymes to assemble a mature PG.

show abstract

Transcriptional Profiling of Coxiella burnetii Reveals Extensive Cell Wall Remodeling in the Small Cell Variant Developmental Form

Cited by 54 publications

References 120 publications

Peptidoglycan in obligate intracellular bacteria

Peptidoglycan in obligate intracellular bacteria

Coxiella burnetii RpoS Regulates Genes Involved in Morphological Differentiation and Intracellular Growth

Building peptidoglycan inside eukaryotic cells: A view from symbiotic and pathogenic bacteria

Contact Info

Product

Resources

About