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Bacterial infections: uncommon presentations.

The essence of dermatology is morphology. The most important instrument in the practice of dermatology has always been, and still is, the naked eye; however, "We see only what we are ready to see, what we have been taught to see" (Jean Martin Charcot). Although most practitioners will easily correctly diagnose common bacterial skin diseases (such as cellulitis, erysipelas, impetigo, etc), only a trained and updated dermatologist will recognize the unusual forms and rare variants of these diseases. Bacterial skin diseases are sometimes acute and life-threatening. The mortality rates from necrotizing fasciitis range from 20% to 40%, to name just one example. It is not unreasonable to expect that dermatologists, whether in clinical practice or in referral centers, will be the first physicians to be confronted with unusual variants of bacterial skin diseases that have been unrecognized by non-dermatologists. Some of these cases might even be life-threatening, and only prompt and early recognition, diagnosis, and treatment can make the difference between losing and saving a patient's life. In short, we dermatologists should hone our clinical diagnostic skills and expand our knowledge of the rare forms and unusual and atypical variants of skin diseases: the textbook variants will probably be recognized and treated by general practitioners.

Cellulitis↗

Porcine enteric spirochete infections in the UK: surveillance data and preliminary investigation of atypical isolates.

Investigations into the possible causes of colitis and typhlocolitis were carried out on 98 pig units in the United Kingdom between 1997 and 1999. Brachyspira pilosicoli was identified most commonly, occurring as the suggested primary agent in 18% of the outbreaks but forming part of mixed infections in another 24% of outbreaks. The equivalent figures for other bacterial pathogens were: B. hyodysenteriae, 13% and 16%; Lawsonia intracellularis, 10% and 15%: Salmonella species, 6% and 12%; and Yersinia species, 4% and 10%. Unclassified Brachyspira species of unknown pathogenicity were identified in 12% of outbreaks. The 24 unclassified isolates divided into three groups on the basis of their phenotypic characteristics. In addition, there were 50 atypical Brachyspira species isolates that showed differences between their phenotypic characteristics and genetic identity based on sequence analysis of a section of the 23S rDNA gene. Four representative atypical isolates were found to be pathogenic as a result of an experimental oral challenge study in pigs.

Animals↗

Serological diagnosis of pertussis: IgM, IgA and IgG antibodies against Bordetella pertussis measured by enzyme-linked immunosorbent assay (ELISA).

Igm, IgA and IgG antibodies against Bordetella pertussis were measured by enzyme-linked immunosorbent assay (ELISA) with an ultrasonicate of formalin-killed bacteria (a mixture of strains 1, 2 and 1, 2, 3) as antigen and disposable polystyrene 9-cuvette blocks as the solid phase. The specificity properties of the assay were assessed by an inhibition technique. Of the microbes tested, only B. parapertussis was able to cause a significant inhibition. In addition, IgM and IgA antibodies against B. pertussis were only found in some sporadic cases of respiratory infections caused by other microbes. Sera, nasal swabs and cough plates were received from 198 patients with suspected whooping-cough. ELISA determinations were mostly made from only one serum sample of each patient. Paired sera were studied only from the culture-positive infants under 3 months of age. The number of positive cultures was highest in group under 3 months of age (41%), where the frequency of positive ELISA was lowest (20%). The use of paired sera strikingly increased the number of ELISA-positive individuals in this youngest patient group. In later life, the relationship between these tests changed: isolation was positive in only about 10% of the patients, whereas 29-64% yielded positive titres in ELISA. This study shows that pertussis ELISA is a valuable aid in the rapid diagnosis of pertussis, particularly of the atypical forms of the disease which mostly are culture-negative.

Antibodies, Bacterial↗

Biogenesis of Fe-S cluster by the bacterial Suf system: SufS and SufE form a new type of cysteine desulfurase.

Biosynthesis of iron-sulfur clusters (Fe-S) depends on multiprotein systems. Recently, we described the SUF system of Escherichia coli and Erwinia chrysanthemi as being important for Fe-S biogenesis under stressful conditions. The SUF system is made of six proteins: SufC is an atypical cytoplasmic ABC-ATPase, which forms a complex with SufB and SufD; SufA plays the role of a scaffold protein for assembly of iron-sulfur clusters and delivery to target proteins; SufS is a cysteine desulfurase which mobilizes the sulfur atom from cysteine and provides it to the cluster; SufE has no associated function yet. Here we demonstrate that: (i) SufE and SufS are both cystosolic as all members of the SUF system; (ii) SufE is a homodimeric protein; (iii) SufE forms a complex with SufS as shown by the yeast two-hybrid system and by affinity chromatography; (iv) binding of SufE to SufS is responsible for a 50-fold stimulation of the cysteine desulfurase activity of SufS. This is the first example of a two-component cysteine desulfurase enzyme.

Alanine↗

[Clinical diagnosis of atopic dermatitis].

Atopic eczema is a pruriginous dermatosis that most often starts before one year, but which may show for the first time after 50 years. The diagnosis is essentially clinical, with signs of banal eczema (especially acute in young infants, more chronic later) but of which the topography develops characteristically as a function of age and in the context of atopy. The development of is chronic, dotted with inflamed eruptions and may be complicated by an alteration of general state with bacterial (very frequent) or viral superinfections. The appearance of asthma is frequent when the dermatosis is extended. It usually disappears before adult age. Differential diagnosis is needed especially when there is an atypical form or association with another pruriginous dermatosis. Questioning must cover the environment, food habits and search for signs that may show the responsibility of an allergen.

Adolescent↗

Action and reaction: Chlamydophila pneumoniae proteome alteration in a persistent infection induced by iron deficiency.

Chlamydophila pneumoniae is an obligate intracellular pathogen implicated in a variety of acute and chronic diseases. Long-term infections are associated with a persistent life stage, in which bacteria can stay for years. They are less accessible to antibiotic treatment but still prone to sustain an inflammatory response. Different in vitro models have been established to mimic and characterize chlamydial persistency. For C. pneumoniae and Chlamydia trachomatis, altered metabolic activities and changed antigenic profiles compared to acute infections have been reported. Most studies including transcriptome and proteome analyses describe persistency induced by IFNgamma treatment. Here, we use iron depletion of the infected cell culture that also leads into persistent infection. We describe differently regulated proteins found by subtractive proteome analysis comparing two early stages of infection with and without addition of the iron chelator deferoxamine-mesylate. While only one bacterial protein was up-regulated during iron deficiency up to 24 h post infection (p.i.), 11 were found to be up-regulated and eight to be down-regulated from 24-48 h p.i. Two down-regulated proteins could be identified by peptide mass fingerprinting as thioredoxin reductase and chromosome partitioning protein (ParB). The latter is involved in chromosome segregation. Thus, using a comparative approach we identified on a proteome level down-regulation of ParB in persistent chlamydial forms, which is in agreement with previous results describing changes in cell division and atypical altered morphology of persistent Chlamydiae.

Amino Acid Sequence↗

Tabetic arthropathy. A report of 43 cases.

Destructive tabetic arthropathy (TA) has become rare in the course of syphilis because of early diagnosis and treatment. TA is difficult to manage because of the severity of the handicap and the absence of a specific treatment. We describe the clinical, biological, and radiological characteristics of TA. In this paper, we performed a retrospective study of 24 patients with TA from 1983 to 2003. Inclusion criteria were typical radiological findings and positive syphilitic serology in blood and/or synovial fluid and/or cerebrospinal fluid. Included in the study were 15 men and 9 women, their mean age was 53.71+/-12.25 years, and the delay of diagnosis was 36.83+/-53.03 months. Thirteen patients (54.2%) had a known primary syphilitis. In the studied cases, 43 of the patients' joints were involved, which concerned knees, hips, the spine, and ankles in 91.66, 8.33, 8.33, and 4.16% of cases, respectively. TA was bilateral in 62.5% and multifocal in 8.3%. The neurological exam found signs suggesting tabes dorsalis in seven cases. The osteoarticular exam showed an abnormal range of mobility (n=25), hydarthrosis, and articular deformation (n=17). Syphilitic serology tests were positive in synovial fluid, cerebrospinal fluid, and blood in 12 (50%), 8 (33.33%), and 24 (100%) cases, respectively. Radiological exam showed atrophic and hypertrophic forms. The frequency and severity of TA in our study may be explained by the frequency of atypical forms of syphilitis and the absence of penicillin in Morocco in the 1950s.

Adult↗

[Chlamydial pathogenesis: diagnostic and therapeutic consequences].

Chlamydiae are among the most common of the human pathogens. Clinical persistence is a key concept in chlamydial pathogenesis. The damaging disease sequelae such as sterility caused by Chlamydia trachomatis and coronary artery disease associated with Chlamydia pneumoniae, are caused by inflammation-based pathology. Although chlamydiacidal antibiotics may kill the bacteria, chlamydial antigens may persist for prolonged period and there is evidence that these non-cultivable forms may lead to continued inflammation. The problem is the difficulty inherent in proving the presence of chronic chlamydial infection. Only nucleic acid amplification test can diagnose these large atypical forms. Clinical treatment failures have been reported and the persistence of the microorganisms raises the question about optimal therapy.

Anti-Bacterial Agents↗

Virulent rough filaments of Listeria monocytogenes from clinical and food samples secreting wild-type levels of cell-free p60 protein.

Atypical rough cell filaments of Listeria monocytogenes (designated FR variants), isolated from clinical and food samples, form long filaments up to 96 microm in length and demonstrated wild-type levels of adherence, invasion, and cytotoxicity to human epithelial HEp-2, Caco-2, and HeLa cells. Unlike previously described avirulent rough mutants of L. monocytogenes that secrete diminished levels of the major extracellular protein p60 and that form long chains that consist of multiple cells of similar size (designated MCR variants), FR variants secreted wild-type or greater levels of p60. This study shows that virulent filamentous forms of L. monocytogenes occur in clinical and food environments and have atypical morphological characteristics compared to those of the wild-type form.

Bacterial Adhesion↗

Occurrence and significance of atypical Aeromonas salmonicida in non-salmonid and salmonid fish species: a review.

Bacterial strains of Aeromonas salmonicida included in the recognized subsp. acromogenes, subsp. masoucida, and subsp. smithia in addition to the large number of strains not included in any of the described subspecies are referred to as atypical A. salmonicida. The atypical strains form a very heterogeneous group with respect to biochemical characteristics, growth conditions, and production of extracellular proteasess. Consequently, the present taxonomy of the species A. salmonicida is rather ambiguous. Atypical A. salmonicida has been isolated from a wide range of cultivated and wild fish species, non-salmonids as well as salmonids, inhabiting fresh water, brackish water and marine environments in northern and central Europe, South Africa, North America, Japan and Australia. In non-salmonid fish species, infections with atypical strains often manifest themselves as superficial skin ulcerations. The best known diseases associated with atypical A. salmonicida are carp Cyprinus carpio erythrodermatitis, goldfish Carassius auratus ulcer disease, and ulcer disease of flounder Platichthys flesus, but atypical strains are apparently involved in more disease outbreaks than previously suspected. Macroscopical and microscopical studies of ulcerated fish indicate internal organs are infrequently invaded by atypical A. salmonicida. This view is supported by the fact that atypical strains are irregularly isolated from visceral organs of ulcerated fish. High mortality caused by atypical A. salmonicida has been observed in populations of wild non-salmonids and farmed salmonids, although the association between the mortality in the wild fish stocks and atypical A. salmonicida has not always been properly assessed. In injection experiments the pathogenicity of the atypical strains examined showed large variation. An extacellular A-layer has been detected in different atypical strains, but virulence mechanisms different from those described for (typical) A. salmonicida subsp. salmonicida, for example an extracellular metallo-protease and a different iron utilization mechanism, have been described. Limited information is available about the ecology, spread and survival of atypical strains in water. The commonly used therapeutic methods for the control of diseases in farmed fish caused by atypical A. salmonicida are generally effective against the atypical strains. Resistance to different antibiotics and transferable plasmid encoding multiple drug resistance have been observed in atpical A. salmonicida. Studies aimed at producing a vaccine against atypical strains are in progress.

Aeromonas↗

Interleukin-1beta responses to Mycoplasma pneumoniae infection are cell-type specific.

Interleukin-1beta (IL-1beta) is a major proinflammatory cytokine that is involved in many important cellular functions such as proliferation, differentiation, and activation of different cell types. Its mature form is released from the cells in response to various bacterial and viral infections, and it plays a significant role in host defense. Mycoplasma pneumoniae is a small bacterium without a cell wall that causes tracheobronchitis and atypical pneumonia in humans following attachment to respiratory epithelium, as well as extrapulmonary infections. Very little is known about the role of cytokines in pathogenesis or the response of target cells to M.pneumoniae attachment. The purpose of this study was to investigate the ability of M. pneumoniae to induce IL-1beta in human lung epithelial carcinoma A549 and in human monocytic U937 cell lines. Following M. pneumoniae infection, both IL-1beta mRNA and protein were induced in A549 cells vs. no induction in uninfected cells; however, the protein remained inside the A549 cells. Similarly, M. pneumoniae infection strongly increased mRNA and extracellular protein levels in U937 cells, which unlike A549 cells did exhibit baseline constitutive levels. De novo IL-1beta protein expression was verified by cycloheximide studies. M. pneumoniae infection did not affect constitutive caspase-1 mRNA or protein levels in either cell line. Reduced caspase-1 activity in A549 cell lysates suggests the presence of an endogenous caspase-1 inhibitory component in the A549 cells. These collective data confirm previous studies that show that M. pneumoniae is a potent inducer of cytokines following adherence to host target cells, and establish that IL-1beta release in response to M. pneumoniae infection is cell-type specific, thus emphasizing the importance of carefully considering multiple cell types in M. pneumoniae pathogenesis studies involving both immune cells and cytokine release patterns.

Bacterial Adhesion↗

Severe clinical forms of cytochrome b-negative chronic granulomatous disease (X91-) in 3 brothers with a point mutation in the promoter region of CYBB.

Chronic granulomatous disease (CGD) is a rare congenital syndrome that results in severe, recurrent bacterial and fungal infections. The most common form is caused by defects in the CYBB gene, leading to the absence of gp91phox associated with totally abolished NADPH oxidase activity (X91(0) CGD). We report 3 brothers with atypical cases of X-linked CGD, characterized by low levels of expression of gp91phox (X91(-) CGD). A point mutation (T-55C) identified in the CYBB gene's promoter region appears to prevent the full expression of this gene in neutrophils. This results in low levels of expression of gp91phox protein that are correlated with residual oxidase activity in the whole population of neutrophils. The total O(2)(-) production in these cells was approximately 5% of normal. Despite this oxidase activity, the patients experienced severe and life-threatening infections. It was concluded that the O(2)(-) production in the neutrophils of these patients was not sufficient to protect them against infections, and this X91(-) CGD phenotype must be considered to be a severe clinical form of CGD.

Base Sequence↗

Heterogeneity of Borrelia burgdorferi in the skin.

The reliability of various in vitro techniques to identify Borrelia burgdorferi infection is still unsatisfactory. Using a high-power resolution videomicroscope and staining with the borrelia genus-specific monoclonal flagellar antibody H9724, we identified borrelial structures in skin biopsies of erythema chronicum migrans (from which borrelia later was cultured), of acrodermatitis chronica atrophicans, and of morphea. In addition to typical borreliae, we noted stained structures of varying shapes identical to borreliae found in a "borrelia-injected skin" model; identical to agar-embedded borreliae; and identical to cultured borreliae following exposure to hyperimmune sera and/or antibiotics. We conclude that the H9724-reactive structures represent various forms of B. burgdorferi rather than staining artifacts. These "atypical" forms of B. burgdorferi may represent in vivo morphologic variants of this bacterium.

Acrodermatitis↗

Aliphatic epoxide carboxylation.

Aliphatic epoxides (epoxyalkanes) are highly reactive electrophilic molecules that are formed from the monooxygenase-catalyzed epoxidation of aliphatic alkenes. The bacterial metabolism of short-chain epoxyalkanes occurs by a three-step pathway resulting in net carboxylation to beta-ketoacids. This pathway uses the atypical cofactor coenzyme M (CoM; 2-mercaptoethanesulfonic acid) as the nucleophile for the epoxide ring opening and as the carrier of 2-hydroxyalkyl- and 2-ketoalkyl-CoM intermediates. Four enzymes are involved in epoxide carboxylation: a zinc-dependent alkyltransferase, two short-chain dehydrogenases with specificities for the chiral products of the R- and S-1,2-epoxyalkane ring opening, and an NADPH:disulfide oxidoreductase/carboxylase that reduces the thioether bond of the 2-ketoalkyl-CoM conjugate and carboxylates the resulting carbanion. In this review, we summarize the biochemical, mechanistic, and structural features of the enzymes of epoxide carboxylation and show how these enzymes, together with CoM, work in concert to achieve this highly unusual carboxylation reaction.

Alkenes↗

[Clinical description of acute pyelonephritis].

Acute pyelonephritis is frequent. Its usual signs and symptoms comprise renal pain, fever, inflammation, and presence of germs and leukocytes in the urine. Primary acute E. coli pyelonephritis is frequent in the young female and in most cases is a benign condition. Atypical pyelonephritis may be painless, or without high fever, or lacking bacterial growth in the urine owing to previous inappropriate treatment. Severe pyelonephritis is mainly observed in diabetic, alcoholic or immunocompromised patients. In occasional cases, a common form of pyelonephritis may develop to formation of a renal abscess requiring drainage. When secondary to urinary tract abnormalities, pyelonephritis may be complicated with septicaemia and can induce early and severe renal tissue damage. This form warrants early urological treatment. The common pyelonephritis of the young female without previous history of febrile urinary tract infection requires little imaging. Conversely, extensive uroradiological workup is mandatory in the very young and the elderly, in the male, when treatment is not rapidly effective or in case or early relapse. In some cases, pyelonephritis leads to the development of cortical scars, the long-term prognosis of which remains to be determined.

Abscess↗

Branhamella catarrhalis: fatty acid and lipopolysaccharide analysis of an atypical strain from blood culture.

A Branhamella catarrhalis-like organism was isolated from blood cultures; it was atypical in showing negative nitrate and nitrite and positive gamma-glutamylaminopeptidase reactions, in agglutinating with Neisseria meningitidis antisera, and in forming butyrous colonies. Cell-wall fatty-acid and lipopolysaccharide analysis provided evidence that this isolate was an atypical B. catarrhalis.

Bacterial Infections↗

The use of fibreoptic bronchoscopy with sterile catheter in the diagnosis of pneumonia.

The use of fibreoptic bronchoscopy with sterile catheter sampling of pulmonary secretions was evaluated in 70 patients with a provisional diagnosis of pneumonia. In 37 patients quantitative analysis of the sterile catheter isolates was performed (colony forming units (CFU) per ml). Potential bacterial pathogens were isolated in 37 patients and in the quantitative analysis, 14 of 22 isolates were grown in counts greater than or equal to 10(3) CFU/ml. Sterile catheter increased the bacterial isolation rate as in only 19 patients blood (2) or sputum (18) cultures yielded the same organisms. Sputum cultures showed a 25% false-positive rate in patients with no growth from sterile catheter. Quantitative analysis did not yield any further information in patients receiving antibiotics. Atypical or fungal pneumonia was diagnosed in 22 patients, while ten patients had other pathology simulating pneumonia. Sterile catheter sampling of pulmonary secretions at fibreoptic bronchoscopy proved to be a valuable tool in the diagnosis of bacterial pneumonia.

Adolescent↗

[Leptospirosis in a Dakar hospital: results of a new survey].

The incidence of leptospirosis in West Africa is still almost unknown. Doubtful or positive serological tests were found in approx. 35% of the patients admitted to the hospital, among which leptospirosis could clinically or biologically be suspected. This rather high proportion reflects the frequency of recent or past contacts with leptospira antigen. It is in agreement with the high infestation prevalence observed among several domestic or wild animals, besides small rodents. On the countrary, it should be noted that the leptospirosis-illness, at least in its pure form, with its characteristic hepatic, renal and neurological signs, is seldom seen. Seven typical cases only (among which five at the hosptical Le Dantec) have been diagnosed in Dakar during these last 6 years. Even taking into account that the proportion of atypical, fruste or undiagnosed forms is not negligible, leptospirosis does not appear to be a major medical problem in Senegal.

Adult↗