The Annexin A2/p11 complex is required for efficient invasion of<i>Salmonella</i> Typhimurium in epithelial cells

Jolly, Carrie; Winfree, Seth; Hansen, Bryan; Steele‐Mortimer, Olivia

doi:10.1111/cmi.12180

Cited by 47 publications

(46 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plastins further participate in cell invasion by the intracellular pathogens Salmonella and Shigella (100). Similarly, AHNAK complexes with actin, S100A10 and annexin A2 to mediate architectural remodeling of the cell membrane and cortical cytoskeleton to promote invasion of Salmonella into epithelial cells (100,(102)(103)(104)(105). We hypothesize that the increased levels of these actin-associated proteins suggest actin remodeling enhances recruitment of immune cells and invasion of epithelial cells.…”

Section: Discussionmentioning

confidence: 96%

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

Harrison

Dubois

John-Williams

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

A thorough understanding of the molecular details of the interactions between bacteria and host are critical to ultimately prevent disease. Recent technological advances allow simultaneous analysis of host and bacterial protein and metabolic profiles from a single small tissue sample to provide insight into pathogenesis. We used the chinchilla model of human otitis media to determine, for the first time, the most expansive delineation of global changes in protein and metabolite profiles during an experimentally induced disease. After 48 h of infection with nontypeable Haemophilus influenzae, middle ear tissue lysates were analyzed by high-resolution quantitative two-dimensional liquid chromatography-tandem mass spectrometry. Dynamic changes in 105 chinchilla proteins and 66 metabolites define the early proteomic and metabolomic signature of otitis media. Our studies indicate that establishment of disease coincides with actin morphogenesis, suppression of inflammatory mediators, and bacterial aerobic respiration. We validated the observed increase in the actin-remodeling complex, Arp2/3, and experimentally showed a role for Arp2/3 in nontypeable Haemophilus influenzae invasion. Direct inhibition of actin branch morphology altered bacterial invasion into host epithelial cells, and is supportive of our efforts to use the information gathered to modify outcomes of disease. The twenty-eight nontypeable Haemophilus influenzae proteins identified participate in carbohydrate and amino acid metabolism, redox homeostasis, and include cell wall-associated metabolic proteins. Quantitative characterization of the molecular signatures of infection will redefine our understanding of host response driven developmental changes during pathogenesis. These data represent the first comprehensive study of host protein and metabolite profiles in vivo in response to infection and show the feasibility of extensive characterization of host protein profiles during disease. Identification of novel protein targets and metabolic biomarkers will advance development of therapeutic and diagnostic options for treatment of disease. Molecular & Cellular Proteomics 15: 10.1074/mcp.M115.052498, 1117-1138, 2016.Our current understanding of the global changes that occur during infection is primarily based upon transcriptional profiles of either the host or the bacteria. However, a significant component of disease progression is dependent upon posttranscriptional processes. Recent advances in the application of two-dimensional tandem mass spectrometry have dramatically increased sensitivity to allow simultaneous analyses of multiple molecules from very small biological samples. In this study, we report the comprehensive proteomic and metabolomic profiling of middle ear tissues using samples that are smaller than those typically obtained from a human biopsy. Proteomic and metabolomic analyses of samples as small as biopsies will revolutionize the elucidation of the mechanisms From the

show abstract

Section: Discussionmentioning

confidence: 96%

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

Harrison

Dubois

John-Williams

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…The expression of AnnexinA2 on the cell surface plays an important role in cell-cell interactions32. Furthermore, it has been shown to be the interacting partner for attachment of various bacteria to epithelial cells (for example, Pseudomonas auroginosa 33, E. coli 34, and Salmonella typhymurium 35). However, contrary to the study published by Jolly et al 35,.…”

Section: Discussionmentioning

confidence: 99%

Clumping factor A of Staphylococcus aureus interacts with AnnexinA2 on mammary epithelial cells

Ashraf

Cheng

Zhao

2017

Sci Rep

View full text Add to dashboard Cite

Staphylococcus aureus is one of major pathogens that can cause a series of diseases in different hosts. In the bovine, it mainly causes subclinical and contagious mastitis, but its mechanisms of infection are not fully understood. Considering the fact that virulence factors play key roles in interactions between the bacterium and host cells, this study aimed to identify if a binding partner of S. aureus clumping factor A (ClfA) exists on the bovine mammary epithelial cells. The ClfA protein was used as a bait to pull down lysates of cultured bovine mammary epithelial cells (MAC-T cells). One pull-down protein was identified through use of mass spectrometry and bioinformatics analyses as bovine AnnexinA2. The Western blot and in vitro binding assay confirmed that the full A domain of ClfA was necessary to bind to AnnexinA2. In addition, the interaction between ClfA and AnnexinA2 was validated biochemically by ELISA with a KD value of 418+/−93 nM. The confocal microscopy demonstrated that ClfA and AnnexinA2 partially co-localized in the plasma membrane and that the majority of them were transported into cytoplasm. Taken together, the results demonstrate that ClfA binds with AnnexinA2 and this interaction could mediate S. aureus invasion into bovine mammary epithelial cells.

show abstract

“…Binding of PspK to annexin A2 was restricted to the R3 domain (AA187-279), further indicating that this was a specific process and was likely to be an essential step for initiating colonization of NESp in the nasopharynx. Annexin A2 is a well-known membrane protein involved in a variety of actin-driven membrane processes, such as phagocytosis, endocytosis, and membrane ruffling, [33][34][35][36]43 and is known to mediate the efficient binding of Salmonella Typhimurium, enteropathogenic Escherichia coli (EPEC), and Mycoplasma pneumoniae toxin to epithelial cells. The predicted amino acid sequence of the R3 domain of PspK has significant homology to the R1 and R2 domains of PspC, a cell wallassociated choline-binding protein.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen

et al. 2017

View full text Add to dashboard Cite

The pneumococcal capsule is indispensable for pathogenesis in systemic infections; however, many pneumococcal diseases, including conjunctivitis, otitis media, and some systemic infections in immunocompromised patients, are caused by nonencapsulated Streptococcus pneumoniae (NESp). Null capsule clade 1 (NCC1), found in group 2 NESp, expresses pneumococcal surface protein K (PspK) and is becoming prevalent among pneumococcal organisms owing to the widespread use of pneumococcal conjugate vaccines. Despite its clinical importance, the molecular mechanisms underlying the prevalence of NCC1 have not been fully elucidated. Here, we investigated the role of the R3 domain of PspK in the epithelial cell adherence of NCC1. We found that the R3 domain of PspK mediated NCC1 adherence via its direct interaction with the epithelial surface protein annexin A2. Additionally, neutralization with purified recombinant PspK-R3 or rabbit anti-UD:R3 IgG inhibited binding of NESp to lung epithelial cells in vitro. Immunization with the 'repeat' domain of PspK-R3 or PspK-UD:R3 effectively elicited mucosal and systemic immune responses against PspK-R3 and provided protection against nasopharyngeal, lung, and middle ear colonization of NESp in mice. Additionally, we found that rabbit anti-UD:R3 IgG bound to PspC-R1 of the encapsulated TIGR4 strain and that UD:R3 immunization provided protection against nasopharyngeal and lung colonization of TIGR4 and deaths by TIGR4 and D39 in mice. Further studies using 68 pneumococcal clinical isolates showed that 79% of clinical isolates showed cross-reactivity to rabbit anti-UD:R3 IgG. About 87% of serotypes in the 13-valent pneumococcal conjugate vaccine (PCV) and 68% of nonvaccine serotypes were positive for cross-reactivity with rabbit anti-UD:R3 IgG. Thus, the R3 domain of PspK may be an effective vaccine candidate for both NESp and encapsulated Sp.

show abstract

The Annexin A2/p11 complex is required for efficient invasion ofSalmonella Typhimurium in epithelial cells

Cited by 47 publications

References 65 publications

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

Clumping factor A of Staphylococcus aureus interacts with AnnexinA2 on mammary epithelial cells

Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen

Contact Info

Product

Resources

About