Complement resistance mechanisms of Klebsiella pneumoniae

Doorduijn, Dennis J.; Rooijakkers, Suzan H.M.; Schaik, Willem van; Bardoel, Bart W.

doi:10.1016/j.imbio.2016.06.014

Cited by 106 publications

(89 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These surface structures mark the interface between individual members of the microbiota (and their host), and thus are likely to play an important role during microorganism–microorganism and microorganism–host interactions in the gut. This is certainly the case for numerous pathogens whose capsules aid in immune system evasion via mechanisms that include disruption of neutrophil chemotaxis (for example, Salmonella typhi 61 ) and evasion of host complement system (for example, Klebsiella pneumoniae 62 ). By contrast, Bacteroides use a process called phase variation that controls the expression of their capsular polysaccharide biosynthetic loci in an on/off manner 63 (Fig.…”

Section: Bacteroides Reveal Microbiota Biochemistrymentioning

confidence: 99%

An insider's perspective: Bacteroides as a window into the microbiome

2017

View full text Add to dashboard Cite

Over the last decade, our appreciation for the contribution of resident gut microorganisms—the gut microbiota—to human health has surged. However, progress is limited by the sheer diversity and complexity of these microbial communities. Compounding the challenge, the majority of our commensal microorganisms are not close relatives of Escherichia coli or other model organisms and have eluded culturing and manipulation in the laboratory. In this Review, we discuss how over a century of study of the readily cultured, genetically tractable human gut Bacteroides has revealed important insights into the biochemistry, genomics and ecology that make a gut bacterium a gut bacterium. While genome and metagenome sequences are being produced at breakneck speed, the Bacteroides provide a significant ‘jump-start’ on uncovering the guiding principles that govern microbiota–host and inter-bacterial associations in the gut that will probably extend to many other members of this ecosystem.

show abstract

Section: Bacteroides Reveal Microbiota Biochemistrymentioning

confidence: 99%

An insider's perspective: Bacteroides as a window into the microbiome

2017

View full text Add to dashboard Cite

show abstract

“…[52][53][54] K. pneumoniae carries a fulllength O antigen resistant toward complementmediated killing, which protects by binding C3b to C3 away from the bacterial membrane leading to a disruption in the membrane attack complex. 55 On the other hand, LPS could also induce strong immune activation by activating TLR4, leading to the release of cytokines and chemokines which result in an influx of neutrophils and macrophages to the site of infection. 56 Upon colonization of the GIT, K. pneumoniae causes insult to the intestinal mucosa by secreting a potent genotoxin called colibactin which is also produced by certain other members of the Enterobacteriaceae family, including E. coli.…”

Section: Pathogenic Mechanisms and Virulence Factors Of K Pneumoniae Imentioning

confidence: 99%

Impact of Klebsiella pneumoniae in lower gastrointestinal tract diseases

Kaur

Vadivelu

Samudi

2018

J of Digest Diseases

View full text Add to dashboard Cite

The 2016 Global Burden of Disease report by WHO revealed that diseases of the gastrointestinal tract (GIT) had one of the highest incidence rates worldwide. The plethora of factors that contribute to the development of GIT-related illnesses can be divided into genetic, environmental and lifestyle factors. Apart from that, the role that infectious agents play in the development of GIT diseases has piqued the interest of researchers worldwide. The human gut harbors approximately 10 bacteria in it with increasing concentration toward the lower GIT. Among the various microbiota that colonize the human gut, Gram-negative bacteria have been most notoriously linked to GIT-related diseases such as inflammatory bowel disease (IBD) including Crohn's disease and ulcerative colitis and colorectal cancer (CRC). Some of the notable culprits that have been attributed to these diseases are Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli and Helicobacter pylori. However, studies in recent years are beginning to recognize a new player, Klebsiella pneumoniae (K. pneumoniae) in the causation and progression of GIT diseases. Once synonymous with infections and diseases of the upper respiratory tract, K. pneumoniae has now emerged as one of the pathogens commonly isolated from patients with GIT diseases. However, extensive studies attributing K. pneumoniae to GIT diseases, particularly that of CRC are scanty. Therefore, this review intends to shed light on the association of K. pneumoniae in gastrointestinal diseases such as Crohn's disease, ulcerative colitis as well as CRC.

show abstract

“…We identified complement-resistant E. coli strains that blocked MAC-mediated killing by preventing efficient anchoring of C5b-7 to the bacterial cell envelope and subsequent insertion of MAC pores. Although several mechanisms of bacterial complement evasion have been described (33–36), these are mostly not MAC-specific because they block initial complement activation steps such as recognition or the deposition of functional convertases (35,37,38). Preventing efficient anchoring of C5b-7 to thus affect insertion of MAC pores into the bacterial cell envelope has not, to our knowledge, been reported before on E. coli .…”

Section: Discussionmentioning

confidence: 99%

Bacterial killing by complement requires direct anchoring of Membrane Attack Complex precursor C5b-7

Doorduijn

Bardoel

Heesterbeek

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

15An important effector function of the human complement system is to directly kill Gram-16 negative bacteria via Membrane Attack Complex (MAC) pores. MAC pores are assembled when 17 surface-bound convertase enzymes convert C5 into C5b, which together with C6, C7, C8 and 18 multiple copies of C9 forms a transmembrane pore that damages the bacterial cell envelope. 19 Recently, we found that bacterial killing by MAC pores requires local conversion of C5 by 20 surface-bound convertases. In this study we aimed to understand why local assembly of MAC 21 pores is essential for bacterial killing. Here, we show that rapid interaction of C7 with C5b6 is 22 required to form bactericidal MAC pores. Binding experiments with fluorescently labelled C6 23 show that C7 prevents release of C5b6 from the bacterial surface. Moreover, trypsin shaving 24 experiments and atomic force microscopy revealed that this rapid interaction between C7 and 25 C5b6 is crucial to efficiently anchor C5b-7 to the bacterial cell envelope and form complete 26 MAC pores. Using complement-resistant clinical E. coli strains, we show that bacterial 27 pathogens can prevent complement-dependent killing by interfering with the anchoring of C5b-7. 28 While C5 convertase assembly was unaffected, these resistant strains blocked efficient anchoring 29 of C5b-7 and thus prevented stable insertion of MAC pores into the bacterial cell envelope. 30 Altogether, these findings provide basic molecular insights into how bactericidal MAC pores are 31 assembled and how bacteria evade MAC-dependent killing. 33When bacteria invade the human body, they are attacked by the immune system that tries to clear 34 the infection. Gram-negative bacteria can be directly killed by the complement system, a family 35 of proteins in blood and bodily fluids, that forms toroid-shaped Membrane Attack Complex 36 (MAC) pores into bacterial membranes (1-4). MAC assembly is initiated when recognition 37 molecules, such as antibodies and lectins, bind to bacterial surface structures and recruit early 38 complement components to the target cell surface. This triggers activation of the complement 39 system, a proteolytic cascade that labels the surface with convertase enzymes that cleave the 40 central components C3 and C5 (5). Conversion of C5 into C5b, by C5 convertases, is a critical 41 first step for the unidirectional step-wise assembly of the MAC pore ( Fig. 1A). Upon formation 42 of C5b, C6 rapidly binds metastable C5b to form a stable C5b6 complex (6). Subsequent 43 association of C7 converts the hydrophilic C5b6 complex into lipophilic C5b-7 that uses an 44 exposed membrane-binding domain of C7 to anchor to the target membrane (7,8). Membrane-45 bound C5b-7 subsequently recruits one copy of C8 and up to 18 copies of C9, which oligomerize 46 and form of a 1.2 MDa transmembrane MAC pore (C5b-9) (9-11). 47Although the molecular steps of MAC assembly have been extensively studied on erythrocytes 48 and model membranes (8,9,(12)(13)(14)(15), the mechanisms by which complement f...

show abstract

Complement resistance mechanisms of Klebsiella pneumoniae

Cited by 106 publications

References 74 publications

An insider's perspective: Bacteroides as a window into the microbiome

An insider's perspective: Bacteroides as a window into the microbiome

Impact of Klebsiella pneumoniae in lower gastrointestinal tract diseases

Bacterial killing by complement requires direct anchoring of Membrane Attack Complex precursor C5b-7

Contact Info

Product

Resources

About