Complement resistance in microbes

Mc, Moffitt; Mm, Frank

doi:10.1007/bf01837364

Cited by 39 publications

(32 citation statements)

References 93 publications

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“…However, while complement-mediated clearance appears to be important in the upper urinary tract (39,42,65), the extent to which complement contributes to bacterial clearance in the bladder remains questionable (38). While we cannot exclude a role for the complement system in eliminating the unencapsulated strain during cystitis, the TLR4-independent loss of fitness of the UPEC K1 capsule mutants may be more attributable to other defects, such as a failure to undergo repeated rounds of intracellular replication in IBC.…”

Section: Discussionmentioning

confidence: 97%

Polysaccharide Capsule and Sialic Acid-Mediated Regulation Promote Biofilm-Like Intracellular Bacterial Communities during Cystitis

et al. 2010

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Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs). A murine UTI model has revealed an infection cascade whereby UPEC undergoes cycles of invasion of the bladder epithelium, intracellular proliferation in polysaccharide-containing biofilm-like masses called intracellular bacterial communities (IBC), and then dispersal into the bladder lumen to initiate further rounds of epithelial colonization and invasion. We predicted that the UPEC K1 polysaccharide capsule is a key constituent of the IBC matrix. Compared to prototypic E. coli K1 strain UTI89, a capsule assembly mutant had a fitness defect in functionally TLR4؉ and TLR4 ؊ mice, suggesting a protective role of capsule in inflamed and noninflamed hosts. K1 capsule assembly and synthesis mutants had dramatically reduced IBC formation, demonstrating the common requirement for K1 polysaccharide in IBC development. The capsule assembly mutant appeared dispersed in the cytoplasm of the bladder epithelial cells and failed to undergo high-density intracellular replication during later stages of infection, when the wild-type strain continued to form serial generations of IBC. Deletion of the sialic acid regulator gene nanR partially restored IBC formation in the capsule assembly mutant. These data suggest that capsule is necessary for efficient IBC formation and that aberrant sialic acid accumulation, resulting from disruption of K1 capsule assembly, produces a NanR-mediated defect in intracellular proliferation and IBC development. Together, these data demonstrate the complex but important roles of UPEC polysaccharide encapsulation and sialic acid signaling in multiple stages of UTI pathogenesis.

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Section: Discussionmentioning

confidence: 97%

Polysaccharide Capsule and Sialic Acid-Mediated Regulation Promote Biofilm-Like Intracellular Bacterial Communities during Cystitis

et al. 2010

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“…Consequently, inflammation, opsonization, and Ab-dependent cellular cytotoxicity (ADCC) but not CDC are likely mechanisms for the prolonged survival seen in the preclinical experiments targeting mucin Ags and suggested in the clinical trials with passively administered and actively induced Abs against mucin Ags. With regard to bacterial infections, this is supported by the severe consequences of hereditary deficiency states involving either the classical or alternate complement pathways and the comparatively trivial consequences to deficiencies of the MAC (49).…”

Section: Discussionmentioning

confidence: 99%

Antibodies against Tumor Cell Glycolipids and Proteins, but Not Mucins, Mediate Complement-Dependent Cytotoxicity

Ragupathi¹,

Liu²,

Musselli³

et al. 2005

The Journal of Immunology

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One of several effector mechanisms thought to contribute to Ab efficacy against cancer is complement-dependent cytotoxicity (CDC). Serological analysis of a series of clinical trials conducted over a 10-year period suggested that six vaccines containing different glycolipids induced Abs mediating CDC whereas four vaccines containing carbohydrate or peptide epitopes carried almost exclusively by mucin molecules induced Abs that did not mediate CDC. To explore this further, we have now compared cell surface reactivity using flow cytometry assays (FACS), complement-fixing ability, and CDC activity of a panel of mAbs and immune sera from these trials on the same two tumor cell lines. Abs against glycolipids GM2, globo H and Lewis Y, protein KSA (epithelial cell adhesion molecule, also known as EpCAM) and mucin Ags Tn, sialylated Tn, Thomsen Friedenreich (TF), and MUC1 all reacted comparably by FACS with tumor cells expressing these Ags. Compared with the strong complement binding and CDC with Abs against glycolipids and KSA, complement binding was diminished with Abs against mucin Ags and no CDC was detected. A major difference between these two groups of Ags is proximity to the cell membrane. Glycolipids and globular glycoproteins extend less than 100 Å from the cell membrane while mucins extend up to 5000 Å. Although complement activation at sites remote from the cell membrane has long been known as a mechanism for resistance from complement lysis in bacteria, it is identified here for the first time as a factor which may contribute to resistance from CDC against cancer cells.

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“…1 and 2). The major function of complement traditionally has been thought to be recognition and elimination of pathogens through direct killing (3) and/or stimulation of phagocytosis (4,5). However, over the last decade the complement system has also been shown to play central immunoregulatory roles such as enhancing humoral immunity (6), modifying T cell immunity (7), shaping the development of the natural Ab repertoire (8), and regulating tolerance to nuclear self Ags such as DNA and chromatin (9,10).…”

Section: Overview Of Complement and Its Biologic Rolesmentioning

confidence: 99%

“…I t has been known for several decades that the complement system plays a central role in the inflammatory response and tissue/organ injury that follows direct immune recognition by Abs as well as in processes such as organ ischemia/ reperfusion (I/R) 3 (reviewed in Ref. 1).…”

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confidence: 99%

The Central Role of the Alternative Complement Pathway in Human Disease

Thurman

Holers

2006

The Journal of Immunology

392

350

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The complement system is increasingly recognized as important in the pathogenesis of tissue injury in vivo following immune, ischemic, or infectious insults. Within the complement system, three pathways are capable of initiating the processes that result in C3 activation: classical, alternative, and lectin. Although the roles that proinflammatory peptides and complexes generated during complement activation play in mediating disease processes have been studied extensively, the relative contributions of the three activating pathways is less well understood. Herein we examine recent evidence that the alternative complement pathway plays a key and, in most instances, obligate role in generating proinflammatory complement activation products in vivo. In addition, we discuss new concepts regarding the mechanisms by which the alternative pathway is activated in vivo, as recent clinical findings and experimental results have provided evidence that continuous active control of this pathway is necessary to prevent unintended targeting and injury to self tissues.

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Complement resistance in microbes

Cited by 39 publications

References 93 publications

Polysaccharide Capsule and Sialic Acid-Mediated Regulation Promote Biofilm-Like Intracellular Bacterial Communities during Cystitis

Polysaccharide Capsule and Sialic Acid-Mediated Regulation Promote Biofilm-Like Intracellular Bacterial Communities during Cystitis

Antibodies against Tumor Cell Glycolipids and Proteins, but Not Mucins, Mediate Complement-Dependent Cytotoxicity

The Central Role of the Alternative Complement Pathway in Human Disease

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