Abscess Formation In Mice Research Articles

A β-Lactamase Responsive Peptide Inhibits MRSA Infection through Self-Assembled Nanonet.

Gram-positive S. aureus is one of the leading pathogens for death associated with antimicrobial resistance. The β-lactamase (Bla) secreted by methicillin-resistant S. aureus (MRSA) hydrolyzes nearly all β-lactam antibiotics, leaving only a few antibiotics available for the clinical treatment of MRSA infections. Thereby, a Bla-responsive peptide (BLAP) is designed here with the capacity of inhibiting MRSA infection through mimicking the host defense mechanism of human defensin-6. The BLAP comprising a self-assembling peptide sequence can respond specifically to the secreted Bla and assemble in situ surrounding MRSA. The assembled nanofibrous network is able to trap MRSA, preventing its invasion into the host cells effectively. As a consequence, the intramuscular injection of BLAP significantly restricted bacterial infection and abscess formation in mice. The biomimetic BLAP holds great potential for the efficient treatment of drug-resistant gram-positive bacterial infections.

Wip1 inhibits neutrophil extracellular traps to promote abscess formation in mice by directly dephosphorylating Coronin-1a.

Neutrophil extracellular traps (NETs) participate in the rapid inhibition and clearance of pathogens during infection; however, the molecular regulation of NET formation remains poorly understood. In the current study, we found that inhibition of the wild-type p53-induced phosphatase 1 (Wip1) significantly suppressed the activity of Staphylococcus aureus (S. aureus) and accelerated abscess healing in S. aureus-induced abscess model mice by enhancing NET formation. A Wip1 inhibitor significantly enhanced NET formation in mouse and human neutrophils in vitro. High-resolution mass spectrometry and biochemical assays demonstrated that Coro1a is a substrate of Wip1. Further experiments also revealed that Wip1 preferentially and directly interacts with phosphorylated Coro1a than compared to unphosphorylated inactivated Coro1a. The phosphorylated Ser426 site of Coro1a and the 28-90 aa domain of Wip1 are essential for the direct interaction of Coro1a and Wip1 and for Wip1 dephosphorylation of p-Coro1a Ser426. Wip1 deletion or inhibition in neutrophils significantly upregulated the phosphorylation of Coro1a-Ser426, which activated phospholipase C and subsequently the calcium pathway, the latter of which promoted NET formation after infection or lipopolysaccharide stimulation. This study revealed Coro1a to be a novel substrate of Wip1 and showed that Wip1 is a negative regulator of NET formation during infection. These results support the potential application of Wip1 inhibitors to treat bacterial infections.

Small-molecule compound SYG-180-2-2 attenuates Staphylococcus aureus virulence by inhibiting hemolysin and staphyloxanthin production.

Multi-drug resistant Staphylococcus aureus infection is still a serious threat to global health. Therefore, there is an urgent need to develop new antibacterial agents based on virulence factor therapy to overcome drug resistance. Previously, we synthesized SYG-180-2-2 (C21H16N2OSe), an effective small molecule compound against biofilm. The aim of this study was to investigate the anti-virulence efficacy of SYG-180-2-2 against Staphylococcus aureus. MIC results demonstrated no apparent antibacterial activity of the SYG-180-2-2. The growth curve assay showed that SYG-180-2-2 had nonlethal effect on S. aureus. Besides, SYG-180-2-2 strongly inhibited the hemolytic activity and staphyloxanthin synthesis in S. aureus. Inhibition of staphyloxanthin by SYG-180-2-2 enhanced the sensitivity of S. aureus to oxidants and human whole blood. In addition, SYG-180-2-2 significantly decreased the expression of saeR-mediated hemolytic gene hlb and staphyloxanthin-related crtM, crtN and sigB genes by quantitative polymerase chain reaction (qPCR). Meanwhile, the expression of oxidative stress-related genes sodA, sodM and katA also decreased. Galleria Mellonella assay revealed that SYG-180-2-2 was not toxic to larvae. Further, the larvae infection model showed that the virulence of bacteria was significantly reduced after 4 μg/mL SYG-180-2-2 treatment. SYG-180-2-2 also reduced skin abscess formation in mice by reducing bacterial burden and subcutaneous inflammation. In conclusion, SYG-180-2-2 might be a promising agent to attenuate the virulence of S. aureus by targeting genes associated with hemolytic activity and staphyloxanthin synthesis.

Staphylococcus aureus lipoproteins promote abscess formation in mice, shielding bacteria from immune killing

Despite being a major bacterial factor in alerting the human immune system, the role of Staphylococcus aureus (S. aureus) lipoproteins (Lpp) in skin infections remains largely unknown. Here, we demonstrated that subcutaneous injection of S. aureus Lpp led to infiltration of neutrophils and monocytes/macrophages and induced skin lesions in mice. Lipid-moiety of S. aureus Lpp and host TLR2 was responsible for such effect. Lpp-deficient S. aureus strains exhibited smaller lesion size and reduced bacterial loads than their parental strains; the altered phenotype in bacterial loads was TLR2-independent. Lpp expression in skin infections contributed to imbalanced local hemostasis toward hypercoagulable state. Depletion of leukocytes or fibrinogen abrogated the effects induced by Lpp in terms of skin lesions and bacterial burden. Our data suggest that S. aureus Lpp induce skin inflammation and promote abscess formation that protects bacteria from innate immune killing. This suggests an intriguing bacterial immune evasion mechanism.

Porphyromonas gingivalis hydrogen sulfide enhances methyl mercaptan-induced pathogenicity in mouse abscess formation.

Porphyromonas gingivalis produces hydrogen sulfide (H2S) from l-cysteine. However, the role of H2S produced by P. gingivalis in periodontal inflammation is unclear. In this study, we identified the enzyme that catalyses H2S production from l-cysteine and analysed the role of H2S using a mouse abscess model. The enzyme identified was identical to methionine γ-lyase (PG0343), which produces methyl mercaptan (CH3SH) from l-methionine. Therefore, we analysed H2S and CH3SH production by P. gingivalis W83 and a PG0343-deletion mutant (ΔPG0343) with/without l-cysteine and/or l-methionine. The results indicated that CH3SH is produced constitutively irrespective of the presence of l-methionine, while H2S was greatly increased by both P. gingivalis W83 and ΔPG0343 in the presence of l-cysteine. In contrast, CH3SH production by ΔPG0343 was absent irrespective of the presence of l-methionine, and H2S production was eliminated in the absence of l-cysteine. Thus, CH3SH and H2S production involves different substrates, l-methionine or l-cysteine, respectively. Based on these characteristics, we analysed the roles of CH3SH and H2S in abscess formation in mice by P. gingivalis W83 and ΔPG0343. Abscess formation by P. gingivalis W83, but not ΔPG0343, differed significantly in the presence and absence of l-cysteine. In addition, the presence of l-methionine did not affect the size of abscesses generated by P. gingivalis W83 and ΔPG0343. Therefore, we conclude that H2S produced by P. gingivalis does not induce inflammation; however, H2S enhances inflammation caused by CH3SH. Thus, these results suggest the H2S produced by P. gingivalis plays a supportive role in inflammation caused by methionine γ-lyase.

EsxA might as a virulence factor induce antibodies in patients with Staphylococcus aureus infection

Staphylococcus aureus (S. aureus) is an important human pathogen, which commonly causes the acquired infectious diseases in the hospital and community. Effective and simple antibiotic treatment against S. aureus-related disease becomes increasingly difficult. Developing a safe and effective vaccine against S. aureus has become one of the world’s hot spots once again. The key issue of developing the vaccine of S. aureus is how to find an ideal key pathogenic gene of S. aureus. It was previously suggested that EsxA might be a very important factor in S. aureus abscess formation in mice, but clinical experimental evidence was lacking. We therefore expressed EsxA protein through prokaryotic expression system and purified EsxA protein by Ni-affinity chromatography. ELISA was used to detect the anti-EsxA antibodies in sera of 78 patients with S. aureus infection and results showed that the anti-EsxA antibodies were positive in the sera of 19 patients. We further analyzed the EsxA positive antibodies related strains by antimicrobial susceptibility assay and found that all of the corresponding strains were multi-drug resistant. Among those multi-drug resistant strains, 73.7% were resistant to MRSA. The results indicated EsxA is very important in the pathogenesis of S. aureus. We suggested that the EsxA is very valuable as vaccine candidate target antigens for prevention and control of S. aureus infection.

Protein A-Specific Monoclonal Antibodies and Prevention of Staphylococcus aureus Disease in Mice

Staphylococcus aureus is a leading cause of human soft tissue infections and bacterial sepsis. The emergence of antibiotic-resistant strains (methicillin-resistant S. aureus [MRSA]) has prompted research into staphylococcal vaccines and preventive measures. The envelope of S. aureus is decorated with staphylococcal protein A (SpA), which captures the Fcγ portion of immunoglobulins to prevent opsonophagocytosis and associates with the Fab portion of V(H)3-type B cell receptors to trigger B cell superantigen activity. Nontoxigenic protein A (SpA(KKAA)), when used as an immunogen in mice, stimulates humoral immune responses that neutralize the Fcγ and the V(H)3(+) Fab binding activities of SpA and provide protection from staphylococcal abscess formation in mice. Here, we isolated monoclonal antibodies (MAbs) against SpA(KKAA) that, by binding to the triple-helical bundle fold of its immunoglobulin binding domains (IgBDs), neutralize the Fcγ and Fab binding activities of SpA. SpA(KKAA) MAbs promoted opsonophagocytic killing of MRSA in mouse and human blood, provided protection from abscess formation, and stimulated pathogen-specific immune responses in a mouse model of staphylococcal disease. Thus, SpA(KKAA) MAbs may be useful for the prevention and therapy of staphylococcal disease in humans.

Comparison of the virulence of exopolysaccharide-producing Prevotella intermedia to exopolysaccharide non-producing periodontopathic organisms.

BackgroundEvidence in the literature suggests that exopolysaccharides (EPS) produced by bacterial cells are essential for the expression of virulence in these organisms. Secreted EPSs form the framework in which microbial biofilms are built.MethodsThis study evaluates the role of EPS in Prevotella intermedia for the expression of virulence. This evaluation was accomplished by comparing EPS-producing P. intermedia strains 17 and OD1-16 with non-producing P. intermedia ATCC 25611 and Porphyromonas gingivalis strains ATCC 33277, 381 and W83 for their ability to induce abscess formation in mice and evade phagocytosis.ResultsEPS-producing P. intermedia strains 17 and OD1-16 induced highly noticeable abscess lesions in mice at 107 colony-forming units (CFU). In comparison, P. intermedia ATCC 25611 and P. gingivalis ATCC 33277, 381 and W83, which all lacked the ability to produce viscous materials, required 100-fold more bacteria (109 CFU) in order to induce detectable abscess lesions in mice. Regarding antiphagocytic activity, P. intermedia strains 17 and OD1-16 were rarely internalized by human polymorphonuclear leukocytes, but other strains were readily engulfed and detected in the phagosomes of these phagocytes.ConclusionsThese results demonstrate that the production of EPS by P. intermedia strains 17 and OD1-16 could contribute to the pathogenicity of this organism by conferring their ability to evade the host's innate defence response.

The Zwitterionic Cell Wall Teichoic Acid of Staphylococcus aureus Provokes Skin Abscesses in Mice by a Novel CD4+ T-Cell-Dependent Mechanism

Zwitterionic polysaccharide (ZPS) components of the bacterial cell envelope have been shown to exert a major histocompatibility complex (MHC) II-dependent activation of CD4+ T cells, which in turn can modulate the outcome and progression of infections in animal models. We investigated the impact of zwitterionic cell wall teichoic acid (WTA) produced by Staphylococcus aureus on the development of skin abscesses in a mouse model. We also compared the relative biological activities of WTA and capsular polysaccharide (CP), important S. aureus pathogenicity factors, in abscess formation. Expression of both WTA and CP markedly affected the ability of S. aureus to induce skin abscess formation in mice. Purified wild-type zwitterionic WTA was more active in inducing abscess formation than negatively charged mutant WTA or purified CP8. To assess the ability of purified native WTA to stimulate T cell proliferation in vitro, we co-cultivated WTA with human T-cells and antigen presenting cells in the presence and absence of various inhibitors of MHC-II presentation. Wild-type WTA induced T cell proliferation to a significantly greater extent than negatively charged WTA. T cell activation was dependent on the presentation of WTA on MHC II, since inhibitors of MHC II-dependent presentation and antibodies to MHC II significantly reduced T cell proliferation. T cells activated in vitro with wild-type WTA, but not negatively charged WTA, induced abscess formation when injected subcutaneously into wild-type mice. CD4−/− mice similarly injected with WTA failed to develop abscesses. Our results demonstrate that the zwitterionic WTA of S. aureus induces CD4+ T-cell proliferation in an MHCII-dependent manner, which in turn modulates abscess formation in a mouse skin infection model. An understanding of this novel T cell-dependent host response to staphylococcal abscess formation may lead to the development of new strategies to combat S. aureus skin and soft tissue infections.

Biofilm-like structures and pathogenicity ofEscherichia hermanniiYS-11, a clinical isolate from a persistent apical periodontitis lesion

Escherichia hermannii, formerly classified as enteric group 11 of Escherichia coli, is considered to be nonpathogenic. In this report, we described some of the pathogenic properties of a viscous material-producing E. hermannii strain YS-11, which was clinically isolated from a persistent apical periodontitis lesion. YS-11 possessed cell surface-associated meshwork-like structures that are found in some biofilm-forming bacteria and its viscous materials contained mannose-rich exopolysaccharides. To further examine the biological effect of the extracellular viscous materials and the meshwork structures, we constructed a number of mutants using transposon mutagenesis. Strain 455, which has a transposon inserted into wzt, a gene that encodes an ATP-binding cassette transporter, lacked the expression of the cell surface-associated meshwork structures and the ability to produce extracellular materials. Complementation of the disrupted wzt in strain 455 with an intact wzt resulted in the restoration of these phenotypes. We also compared these strains in terms of their ability to induce abscess formation in mice as an indication of their pathogenicity. Strains with meshwork-like structures induced greater abscesses than those induced by strains that lacked such structures. These results suggest that the ability to produce mannose-rich exopolysaccharides and to form meshwork-like structures on E. hermannii might contribute to its pathogenicity.

Correlation between Klebsiella pneumoniae carrying pLVPK-derived loci and abscess formation

Klebsiella pneumoniae-caused liver abscess (KLA) is an emerging infectious disease. However, factors other than K1-specific loci that contribute to the pathogenesis of this disease have not been identified. pLVPK is a 219,385-bp plasmid of K. pneumoniae CG43, an invasive K2 strain associated with KLA. We aimed in this study to evaluate the involvement of pLVPK in K. pneumoniae virulence and its clinical significance in abscess formation. A pLVPK-cured CG43 was isolated and its virulence was examined in a mouse model. The prevalence of pLVPK-derived loci terW, iutA, rmpA, silS, and repA was investigated in 207 clinical isolates by screening with specific primers. Loss of pLVPK abolished the ability of K. pneumoniae to disseminate into extraintestinal sites and, consequently, attenuated abscess formation in mice. Primary K. pneumoniae abscess isolates (n = 94) were more likely to be terW (+)-iutA (+)-rmpA (+)-silS (+) than those related to non-abscess infections (n = 113) (62% vs. 27%; p < 0.0001). Logistic regression analysis indicated that the presence of the terW-rmpA-iutA-silS loci was a significant risk factor (odds ratio, 4.12; 95% confidence interval, 2.02-8.4; p < 0.0001) for abscess formation. pLVPK is a determinant for K. pneumoniae virulence and infection with strains carrying the pLVPK-derived terW-rmpA-iutA-silS loci may predispose patients to abscess formation.

Type I Streptococcus pneumoniae carbohydrate utilizes a nitric oxide and MHC II‐dependent pathway for antigen presentation

Some pathogenic bacteria form thick capsules that both block immune responses through inhibition of complement deposition and phagocytosis and stimulate a weak response resulting from a lack of T-cell involvement. Contrary to this model, capsular polysaccharides from 23 serotypes of Streptococcus pneumoniae have been successfully used in a multivalent vaccine in the absence of a carrier protein. Furthermore, type I pneumococcal polysaccharide (Sp1) has been shown to activate T cells in vivo and in vitro via an uncharacterized mechanism. In the present report, we demonstrate that Sp1 utilizes the major histocompatibility complex (MHC) class II pathway in antigen-presenting cells (APCs) for processing and presentation. APCs internalize and process Sp1 through a nitric oxide-dependent mechanism and, once inside the cell, it associates with MHC II proteins in an H-2M-dependent manner that leads to in vivo T-cell activation. These results establish that Sp1 activates T cells which can lead to abscess formation in mice through an H-2M-dependent polysaccharide antigen presentation pathway in APCs, potentially contributing to pneumococcal polysaccharide vaccine efficacy through the recruitment of T-cell help.

Gene expression profile and pathogenicity of biofilm-forming Prevotella intermedia strain 17.

BackgroundPrevotella intermedia (P. intermedia), a gram-negative, black-pigmented anaerobic rod, has been implicated in the development of chronic oral infection. P. intermedia strain 17 was isolated from a chronic periodontitis lesion in our laboratory and described as a viscous material producing strain. The stock cultures of this strain still maintain the ability to produce large amounts of viscous materials in the spent culture media and form biofilm-like structures. Chemical analyses of this viscous material showed that they were mainly composed of neutral sugars with mannose constituting 83% of the polysaccharides. To examine the biological effect of the extracellular viscous materials, we identified and obtained a naturally-occurring variant strain that lacked the ability to produce viscous materials in vitro from our stock culture collections of strain 17, designated as 17-2. We compared these two strains (strains 17 versus 17-2) in terms of their capacities to form biofilms and to induce abscess formation in mice as an indication of their pathogenicity. Further, gene expression profiles between these two strains in planktonic condition and gene expression patterns of strain 17 in solid and liquid cultures were also compared using microarray assays.ResultsStrain 17 induced greater abscess formation in mice as compared to that of the variant. Strain 17, but not 17-2 showed an ability to interfere with the phagocytic activity of human neutrophils. Expression of several genes which including those for heat shock proteins (DnaJ, DnaK, ClpB, GroEL and GroES) were up-regulated two to four-fold with statistical significance in biofilm-forming strain 17 as compared to the variant strain 17-2. Strain 17 in solid culture condition exhibited more than eight-fold up-regulated expression levels of several genes which including those for levanase, extracytoplasmic function-subfamily sigma factor (σE; putative) and polysialic acid transport protein (KpsD), as compared to those of strain 17 in liquid culture media.ConclusionThese results demonstrate that the capacity to form biofilm in P. intermedia contribute to their resistance against host innate defence responses.

Effect of colchicine on the murine immune response induced by Aggregatibacter actinomycetemcomitans

The aim of the present study was to test the hypothesis that colchicine may alter Aggregatibacter actinomycetemcomitans-induced immune response and abscess formation in mice. BALB/c mice were either sham-immunized or immunized with heat-killed A. actinomycetemcomitans. Spleen cells were stimulated with heat-killed A. actinomycetemcomitans in the presence or absence of colchicine. Specific IgG subclass antibodies, interferon-γ (IFN-γ), interleukin-4 (IL-4) and cell proliferation were determined. The animals were sham-immunized (group I) or immunized with heat-killed A. actinomycetemcomitans (groups II–VII). Colchicine was administered intraperitoneally before (group III), on the same day of (group IV), or after (group V) the primary immunization and on the same day of (group VI) or after (group VII) the secondary immunization. All groups were challenged with viable A. actinomycetemcomitans. The levels of serum-specific IgG subclasses and both IFN-γ and IL-4 before and after bacterial challenge were assessed. The diameter of skin lesions was assessed. The results showed that colchicine augmented splenic-specific IgG1 and IL-4 as well as cell proliferation but suppressed specific IgG2a and IFN-γ levels. Enhancement of serum-specific IgG1 and IL-4 levels, suppression of specific IgG2a and IFN-γ levels as well as DTH response, and delayed healing of the lesions were observed in groups IV and VI, but not in the remaining groups of animals. Therefore, these results suggest that colchicine may induce a T helper 2 (Th2)-like immunity specific to A. actinomycetemcomitans in vitro and that colchicine administered on the same day as the immunization may stimulate a non-protective Th2-like immunity in A. actinomycetemcomitans-induced infections in mice.

A novel exopolysaccharide from a clinical isolate of Prevotella nigrescens: purification, chemical characterization and possible role in modifying human leukocyte phagocytosis

Prevotella nigrescens, a gram-negative black-pigmented anaerobic rod, has frequently been isolated from periodontitis and periapical periodontitis lesions. We have isolated an exopolysaccharide-producing P. nigrescens, strain 22, from a chronic periodontitis lesion. The purpose of this study was to determine the chemical composition and function of the exopolysaccharide associated with this clinical isolate. The chemical composition and structure of the purified exopolysaccharide from strain 22 were determined by high performance liquid chromatography and methylation analysis. To define the biological function of this exopolysaccharide, a chemically induced exopolysaccharide nonproducing mutant, strain 328, which was derived from strain 22, was established. The biological effects of exopolysaccharide were determined by comparing the ability of strain 22, strain 328 or heat-killed strain 22 to form abscesses in mice and to interfere with the phagocytic activity of peripheral blood polymorphonuclear leukocytes. Chemical analysis showed that isolated exopolysaccharide consisted of mannose (521.6 microg/mg), glucose (25.6 microg/mg), fructose (65.8 microg/mg), galactose (12.5 microg/mg), arabinose (6.2 microg/mg), xylose (3.2 microg/mg), rhamnose (6.1 microg/mg), and ribose (0.6 microg/mg). Methylation analysis of exopolysaccharide indicated that the linkages of mannose were primarily (1-->2, 1-->6) (1-->2) (1-->6), and (1-->3). Strain 22 and, to a lesser extent, its heat-killed counterpart induced greater abscess formation in mice than strain 328, even though the enzymatic profile of strain 22 was similar to that of strain 328. The ability of strain 328 to induce abscess formation was restored by adding the purified exopolysaccharide isolated from strain 22 to the cell suspension of strain 328. Exopolysaccharide alone failed to induce abscess formation in mice. Further, strain 328 but not the untreated or heat-killed strain 22, was phagocytosed by polymorphonuclear leukocytes both in the presence and in the absence of opsonic factors. The results suggest that these polysaccharides isolated from strain 22, which primarily consisted of mannose, may play a key role in the development of the chronic inflammatory lesion from which this strain was isolated.

Treponemal Phospholipids Inhibit Innate Immune Responses Induced by Pathogen-associated Molecular Patterns

Host innate immune responses to microbial components, known as pathogen-associated molecular patterns (PAMPs), are regulated and modified by cellular receptors and serum proteins, including Toll-like receptors (TLRs), CD14, and LPS-binding protein (LBP). We demonstrated that a treponemal membrane lipid inhibited PAMPs-induced immune responses. The chemical structure of the lipid was elucidated as a phosphatidylglycerol (PG) derivative, which is scarce in most mammalian tissues, but relatively abundant in treponemal membrane lipids. Natural and synthetic PG counterparts as well as related natural anionic phospholipids, phosphatidylinositol, phosphatidylserine, and cardiolipin, also demonstrated an inhibitory effect. Further, we noted that PG inhibited PAMPs-induced immune responses by blocking the binding of PAMPs with LBP and CD14. In addition, PG decreased proinflammatory cytokine production in serum of LPS-injected mice and depressed abscess formation in mice infected with treponemes. These results suggest that treponemal phospholipid interfere the function of LBP/CD14 and act as a modulator of innate immune responses.

Inhibition of Macrophage Procoagulant Activity with Lipids Reduces Infra-Abdominal Abscess Formation in Mice

Macrophage procoagulant activity (PCA) has been proposed as a critical element in the formation of intra-abdominal abscesses. We tested the ability of local and systemic lipids (a known PCA inhibitor in vitro) to alter both peritoneal macrophage PCA and mixed Escherichia coli/Bacteroides fragilis intra-abdominal abscess formation in vivo. Lipids given intraperitoneally inhibited measured inducible peritoneal macrophage PCA for 8 h, and, in other animals, significantly decreased the number of abscesses formed and prevented abscesses in 29% of animals. Parallel experiments using subcutaneous intralipids did not show these effects. These results support the hypothesis that macrophage PCA produced locally is critical for intraperitoneal abscess formation.

The effects of RU 41.740, a glycoprotein immunomodulating agent derived from Klebsiella pneumoniae, on intra-abdominal abscess formation in mice.

The prophylactic and therapeutic efficacies of the immunomodulating agent RU 41.740 (a glycoprotein extract from Klebsiella pneumoniae) were studied in a murine model of intra-abdominal abscess formation with Bacteroides fragilis, Escherichia coli, and bran as an abscess-potentiating agent. Parenteral injection of RU 41.740, either before or after injection of an abscess-inducing mixture (AIM), was associated with significantly diminished incidence and size of abscesses. Abscess incidence and size were significantly decreased by oral administration of RU 41.740 after, but not before, AIM injection. Abscess formation and resolution are the results of complex interactions of host defence mechanisms with bacteria and potentiating agent, and RU 41.740 has been shown previously to activate both macrophage and neutrophil function. These results indicate that activation of non-specific defences may protect against abscess development in chronic sepsis.

The role of Escherichia coli haemolysin in the pathogenic synergy of colonic bacteria in subcutaneous abscess formation in mice

The growth of nine species of colonic bacteria--Escherichia coli, Enterococcus faecalis, Bacteroides ovatus, Fusobacterium varium, Clostridium perfringens, Klebsiella pneumoniae, Proteus vulgaris, Staphylococcus aureus and Bifidobacterium adolescentis--was examined after concomitant injection to form experimental subcutaneous abscesses in mice. Injection of a mixture of c. 10(5) cfu of each of the first five strains (E. coli, Ent. faecalis, B. ovatis, F. varium and C. perfringens) resulted in abscess formation in all mice tested when the E. coli strain was haemolytic. E. coli and B. ovatus multiplied and reached a maximum population of c. 10(8) cfu/abscess. When non-haemolytic E. coli was used, injection of greater than or equal to 10(7) cfu was required for abscess formation. The inclusion of partially purified E. coli haemolysin (125 HU50) with c. 10(5) cfu of bacteria including non-haemolytic E. coli resulted in abscess formation in most mice tested. These results indicate that E. coli haemolysin is one factor that may potentiate pathogenic synergy among colonic bacteria especially between E. coli and B. ovatus, during abscess formation.

Pathogenicity of Staphylococcus lugdunensis, Staphylococcus schleiferi, and three other coagulase-negative staphylococci in a mouse model and possible virulence factors

Staphylococcus lugdunesis and Staphylococcus schleiferi, two newly described species, have been isolated from numerous types of human infections. We compared the pathogenicity of 30 strains of S. lugdunensis, S. schleiferi, Staphylococcus epidermidis, Staphylococcus warneri, and Staphylococcus hominis, using a mouse model in which a foreign body preadhered with the test strain was implanted subcutaneously, followed by injection of the test strain. All five species of staphylococci produced abscesses. Staphylococcus epidermidis, S. schleiferi, and S. lugdunensis yielded species means of 76-91% abscess formation; 80-100% of the infected foreign bodies and tissues were culture positive. These three species were more virulent than S. warneri or S. hominis, which produced abscesses in 54 and 65% of mice, respectively; only 10-48% of the infected samples were culture positive. Transmission electron microscopy of pure cultures of selected strains showed that all species possessed glycocalyx. All species produced a variety of possible virulence factors, such as alpha and delta hemolysins, as well as the aggressins lipase and esterase. The production of exoenzymes did not always correlate with virulence as demonstrated by abscess formation in mice.