The BB0345 Hypothetical Protein of Borrelia burgdorferi Is Essential for Mammalian Infection

Graham, Danielle E.; Groshong, Ashley M.; Jackson-Litteken, Clay D.; Moore, Brendan P.; Caimano, Melissa J.; Blevins, Jon S.

doi:10.1128/iai.00472-20

Cited by 4 publications

(3 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10A ) or in media diluted 1:10 in 1× p hosphate- b uffered s aline (PBS) to simulate nutrient-limited conditions ( Fig. 10B ) ( 111 , 112 ). As expected, BtΔ cdaA C-cis (G175A) and BtΔ cdaA C-cis (G175A) :: cdaA C-cis (WT) strains exhibited an increased growth rate in standard mBSK relative to the BtWT strain (see Fig.…”

Section: Resultsmentioning

confidence: 99%

The Diadenylate Cyclase CdaA Is Critical for Borrelia turicatae Virulence and Physiology

et al. 2021

Self Cite

View full text Add to dashboard Cite

Relapsing fever (RF), caused by spirochetes of the genus Borrelia, is a globally distributed, vector-borne disease with high prevalence in developing countries. To date, signaling pathways required for infection and virulence of RF Borrelia spirochetes are unknown. Cyclic di-AMP (c-di-AMP), synthesized by diadenylate cyclases (DACs), is a second messenger predominantly found in Gram-positive organisms that is linked to virulence and essential physiological processes. Although Borrelia is Gram-negative, it encodes one DAC (CdaA), and its importance remains undefined. To investigate the contribution of c-di-AMP signaling in the RF bacterium, Borrelia turicatae, a cdaA mutant was generated. The mutant was significantly attenuated during murine infection, and genetic complementation reversed this phenotype. Because c-di-AMP is essential for viability in many bacteria, whole genome sequencing was performed on cdaA mutants, and single nucleotide polymorphisms identified potential suppressor mutations. Additionally, conditional mutation of cdaA confirmed that CdaA is important for normal growth and physiology. Interestingly, mutation of cdaA did not affect expression of homologs of virulence regulators whose levels are impacted by c-di-AMP signaling in the Lyme disease bacterium, Borrelia burgdorferi. Finally, the cdaA mutant had a significant growth defect when grown with salts, at decreased osmolarity, and without pyruvate. While the salt treatment phenotype was not reversed by genetic complementation, possibly due to suppressor mutations, growth defects at decreased osmolarity and in media lacking pyruvate could be attributed directly to cdaA inactivation. Overall, these results indicate CdaA is critical for B. turicatae pathogenesis and link c-di-AMP to osmoregulation and central metabolism in RF spirochetes.

show abstract

Section: Resultsmentioning

confidence: 99%

The Diadenylate Cyclase CdaA Is Critical for Borrelia turicatae Virulence and Physiology

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Proteinase K accessibility assays were performed as previously described, with some modification ( 105 ). Stationary-phase cultures were pelleted and resuspended in PBS supplemented with 5 mM MgCl 2 to an optical density at 600 nm (OD 600 ) of 2.5.…”

Section: Methodsmentioning

confidence: 99%

InvL, an Invasin-Like Adhesin, Is a Type II Secretion System Substrate Required for Acinetobacter baumannii Uropathogenesis

Jackson-Litteken

Venanzio

et al. 2022

mBio

Self Cite

View full text Add to dashboard Cite

show abstract

“…Proteinase K accessibility assays. Proteinase K accessibility assays were performed as previously described with some modification (102). Stationary phase cultures were pelleted and resuspended in PBS supplemented with 5 mM MgCl2 to 2.5 OD600.…”

Section: Murine Infection Experiments Animal Experiments Were Approve...mentioning

confidence: 99%

InvL, an invasin-like adhesin, is a type II secretion system substrate required for Acinetobacter baumannii uropathogenesis

Jackson-Litteken

Venanzio

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Acinetobacter baumannii is an opportunistic pathogen of growing concern, as isolates are commonly multidrug resistant. While A. baumannii is most frequently associated with pulmonary infections, a significant proportion of clinical isolates come from urinary sources, highlighting its uropathogenic potential. The type IIsecretion system (T2SS) of commonly used model Acinetobacter strains is important for virulence in various animal models, but the potential role of the T2SS in urinary tract infection (UTI) remains unknown. Herein, we used a catheter-associated UTI (CAUTI) model to demonstrate that a modern urinary isolate, UPAB1, requires the T2SS for full virulence. A proteomic screen to identify putative UPAB1 T2SS effectors revealed an uncharacterized lipoprotein with structural similarity to the intimin-invasin family, which serve as type Vsecretion system (T5SS) adhesins required for the pathogenesis of several bacteria. This protein, designated InvL, lacked the β-barrel domain associated with T5SSs, but was confirmed to require the T2SS for both surface localization and secretion. This makes InvL the first identified T2SS effector belonging to the intimin-invasin family. InvL was confirmed to be an adhesin, as the protein bound to extracellular matrix components and mediated adhesion to urinary tract cell lines in vitro. Additionally, the invL mutant was attenuated in the CAUTI model, indicating a role in Acinetobacter uropathogenesis. Finally, bioinformatic analyses revealed that InvL is present in nearly all clinical isolates belonging to international clone 2, a lineage of significant clinical importance. In all, we conclude that the T2SS substrate InvL is an adhesin required for A. baumannii uropathogenesis.IMPORTANCEWhile pathogenic Acinetobacter can cause various infections, we recently found that 20% of clinical isolates come from urinary sources. Despite the clinical relevance of Acinetobacter as a uropathogen, few virulence factors involved in urinary tract colonization have been defined. Herein, we identify a novel type II secretion system effector, InvL, which is required for full uropathogenesis by a modern urinary isolate. Though InvL has predicted structural similarity to the intimin-invasin family of autotransporter adhesins, InvL is predicted to be anchored to the membrane as a lipoprotein. Similar to other invasin homologs however, we demonstrate that InvL is a bona fide adhesin capable of binding extracellular matrix components and mediating adhesion to urinary tract cell lines. In all, this work establishes InvL as an adhesin important for Acinetobacter’s urinary tract virulence, and represents the first report of a type II secretion system effector belonging to the intimin-invasin family.

show abstract

The BB0345 Hypothetical Protein of Borrelia burgdorferi Is Essential for Mammalian Infection

Cited by 4 publications

References 108 publications

The Diadenylate Cyclase CdaA Is Critical for Borrelia turicatae Virulence and Physiology

The Diadenylate Cyclase CdaA Is Critical for Borrelia turicatae Virulence and Physiology

InvL, an Invasin-Like Adhesin, Is a Type II Secretion System Substrate Required for Acinetobacter baumannii Uropathogenesis

InvL, an invasin-like adhesin, is a type II secretion system substrate required for Acinetobacter baumannii uropathogenesis

Contact Info

Product

Resources

About