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Biomedical subjects

C Lacroix

Publications and source records attributed to C Lacroix.

At least 19 recordsLinked to original sources

Pneumocystis carinii pneumonia in patients with hematologic malignancies: a descriptive study.

Objectives. A retrospective multicentric study was conducted over a five-year period to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating hematologic malignancies.Results. The study included 60 HIV-negative patients with 18 non-Hodgkin's malignant lymphoma (30%), 13 chronic lymphocytic leukaemia (21.7%), 10 acute leukemia (16.6%), 5 multiple myeloma (8.3%), 4 Waldenström's diseases (6.6%), 4 chronic myeloid leukemia (6.6%), 3 myelodysplasia (5%), 2 Hodgkin's diseases (3.3%) and 1 thrombopenia. Bronchoalveolar lavage was diagnostic in all patients. Forty-nine patients received cytotoxic drugs (81.7%), 25 (41.7%) a long-term corticotherapy and 15 (25%) underwent bone marrow transplantation. Twenty-seven patients (45%) required admission in the intensive care unit, 35 (58.3%) received an adjunctive corticotherapy and 18 mechanical ventilation (30%). Twenty patients (33.3%) died of PCP. A previous long-term corticotherapy (p=0.04), high respiratory (p=0.05) and pulse rates (p=0.02), elevated C reactive protein (p=0.01) and mechanical ventilation (OR=13.37; IC: 1.9-50) were associated with a poor prognosis. Adjunctive corticotherapy did not modify the prognosis.Conclusions. These results suggest that PCP can occur during the course of various hematologic malignancies, not only lymphoproliferative disorders. Prognosis remains poor. The diagnosis should be advocated more frequently and earlier to improve the prognosis.

Adult↗

Kinetics of plasma and erythrocyte metformin after acute administration in healthy subjects.

OBJECTIVES: Although the existence of a deep compartment for metformin has long been hypothesized, there is still little direct information concerning metformin distribution in individual tissues in man. The only available study involves chronic metformin therapy. In that study, the measurement of metformin in erythrocytes provided a reliable indicator of metformin distribution and of potential accumulation. To determine the kinetics of metformin in plasma and in erythrocytes after acute oral administration, we performed the present study in healthy subjects after a single oral dose of metformin and compared the pharmacokinetics parameters in erythrocytes to those in plasma. METHODS: Six nondiabetic participants took the study dose of 850 mg metformin at 8: 00 AM after a non-standardized breakfast (i.e., as recommended in clinical practice). Blood samples were collected for metformin measurement in plasma and in erythrocytes at 0, 1, 2, 3, 4, 6, 9, 24, 33, 48, 57, and 72 h. RESULTS: Maximum metformin concentration was attained at 3.0 +/- 0.3 h in plasma and 4.7 +/- 0.5 h in erythrocytes. This difference was not significant. Metformin concentrations peaked at a maximum almost 6 times higher in plasma than in erythrocytes (1.7 +/- 0.1 and 0.3 +/- 0.0 mg/l, respectively). However, because the elimination half-life of metformin was much longer in erythrocytes (23.4 +/- 1.9 h vs. 2.7 +/- 1.2 h), there was no difference in area under the curve between plasma and erythrocytes. The distribution volume (plasma) was calculated to be 146 +/- 11 l. Plasma and erythrocytes concentration-time curves showed that metformin was not detectable in plasma 24 hours after the oral administration, while it remained detectable in erythrocytes up to 48 hours. Metformin concentrations crossed approximately 13 hours after having reached their maximum values in plasma, approximately 16 h after metformin intake. CONCLUSION: Having demonstrated the rapid elimination of metformin from plasma and its slow disappearance from erythrocytes, the presents results should contribute to adjustment of metformin dosage to renal function, assessment of drug compliance, and retrospective analysis (when blood samples are drawn with delay) of the link between metformin and development of lactic acidosis. Most importantly, the present findings should help to ascertain the optimal dosage of metformin, particularly in elderly patients.

Adult↗

Measurement of metformin concentration in erythrocytes: clinical implications.

AIMS: Although pharmacokinetics studies have long suggested a deep compartment for the antidiabetic drug metformin, there is still little information concerning metformin accumulation by individual tissues in man. In the present study, the erythrocyte was chosen to represent this putative deep compartment and metformin concentration in erythrocytes (EM) was compared with that in plasma (PM) to delineate clinical implications. METHODS: A reference group of 58 patients with well-tolerated metformin treatment was studied to provide standard mean metformin concentrations in the fasting state. Secondly, to provide transverse data reflecting clinical practice, the authors reviewed an investigation group of 93 metformin-treated patients with available PM and EM, which had been requested either to adjust metformin dosage to renal function, or to screen for potential metformin accumulation following renal failure, metformin overdose or lactic acidosis. Thirdly, the case of an individual with major metformin accumulation was studied to provide information about metformin elimination. RESULTS: From the bulk of data, we performed three types of analyses: (1) PM and EM were compared. In the investigation group, this comparison was extended to subgroups separated according to low-to-normal, moderately increased or highly increased metformin concentration. (2) Correlative analyses of PM, EM and serum creatinine were performed. (3) A kinetic study of the spontaneous decline of PM and EM was conducted. PM and EM were, respectively, 0.5 +/- 0.4 mg/l and 0.8 +/- 0.4 mg/l in the reference group, and 11.7 +/- 17.8 mg/l (mean +/- SD, range 0.0-71.9 mg/l) and 7.5 +/- 9.4 mg/l (0.0-34 mg/l) in the investigation group, mean serum creatinine of which was 290 +/- 258 micro mol/l. In the low-to-normal PM subgroup (n = 28), PM and EM were, respectively, 0.39 +/- 0.38 mg/l and 0.84 +/- 0.68 mg/l (p < 0.001). In the moderately increased PM subgroup (from therapeutic concentrations +2 SD to 5 mg/l, n = 24), PM and EM were 2.82 +/- 1.13 mg/l and 2.72 +/- 2.03 mg/l (NS). In the sharply increased PM subgroup (> 5 mg/l, n = 41), PM and EM were 27.6 +/- 23.2 mg/l and 17.0 +/- 11.4 mg/l (p = < 0.001). PM and EM were tightly correlated (r = 0.72 in the reference group and r = 0.90 in the investigation group, p < 0.001 for both). Metformin concentrations were also correlated with those of serum creatinine, but more so in the investigation group; in subgroups, a positive correlation was found only at high metformin concentrations and in erythrocytes. The kinetic study performed in the patient with major metformin accumulation showed that PM and EM dropped within less than 3 days from a maximum concentration of 80.0 mg/l and 20.4 mg/l, respectively, to 0.67 mg/l and 6.52 mg/l. CONCLUSIONS: In conclusion, metformin appears to accumulate in erythrocytes and, consequently, may be part of a deep compartment for the drug. This evidence of slow decline in erythrocyte metformin concentration may contribute to retrospective diagnosis of metformin accumulation and to refinements in adjusting metformin dosage to renal function.

Adult↗

Impact of nisin producing culture and liposome-encapsulated nisin on ripening of Lactobacillus added-Cheddar cheese.

This study aimed to evaluate the effects of incorporating liposome-encapsulated nisin Z, nisin Z producing Lactococcus lactis ssp. lactis biovar. diacetylactis UL719, or Lactobacillus casei-casei L2A adjunct culture into cheese milk on textural, physicochemical and sensory attributes during ripening of Cheddar cheese. For this purpose, cheeses were made using a selected nisin tolerant cheese starter culture. Proteolysis, free fatty acid production, rheological parameters and hydrophilic/hydrophobic peptides evolution were monitored over 6 mo ripening. Sensory quality of cheeses was evaluated after 6 mo. Incorporating the nisin-producing strain into cheese starter culture increased proteolysis and lipolysis but did not significantly affect cheese rheology. Liposome-encapsulated nisin did not appear to affect cheese proteolysis, rheology and sensory characteristics. The nisinogenic strain increased the formation of both hydrophilic and hydrophobic peptides present in the cheese water extract. Sensory assessment indicated that acidic and bitter tastes were enhanced in the nisinogenic strain-containing cheese compared to control cheese. Incorporating Lb. casei and the nisinogenic culture into cheese produced a debittering effect and improved cheese flavor quality. Cheeses with added Lb. casei and liposome-encapsulated nisin Z exhibited the highest flavor intensity and were ranked first for sensory characteristics.

Cheese↗

Bifidobacterium longum ATCC 15707 cell production during free- and immobilized-cell cultures in MRS-whey permeate medium.

Bifidobacterium longum ATCC 15707 cell production was studied in MRS medium supplemented with whey permeate (MRS-WP) during free-cell batch fermentations and continuous immobilized-cell cultures. Very high populations were measured after 12 h batch cultures in MRS-WP medium controlled at pH 5.5 (1.7+/-0.5x10(10) cfu/ml), approximately 2-fold higher than in non-supplemented MRS. Our study showed that WP is a low-cost source of lactose and other components that can be used to increase bifidobacteria cell production in MRS medium. Continuous fermentation in MRS-WP of B. longum immobilized in gellan gum gel beads produced the highest cell concentrations in the effluent (4.9+/-0.9x10(9) cfu/ml) at a dilution rate (D) of 0.5 h(-1). However, maximal volumetric productivity (6.9+/-0.4x10(9) cfu ml(-1)h(-1)) during continuous cultures was obtained at D =2.0 h(-1), and was approximately 9.5-fold higher than during free-cell batch cultures at an optimal pH of 5.5 (7.2x10(8) cfu ml(-1)h(-1)).

Bifidobacterium↗

Analysis of underlying diseases and prognosis factors associated with Pneumocystis carinii pneumonia in immunocompromised HIV-negative patients.

The aim of this retrospective study was to determine the underlying diseases associated with Pneumocystis carinii pneumonia (PCP) in immunocompromised HIV-negative patients and to identify prognosis factors in this population. One hundred three cases of PCP were diagnosed over a 5-year period. Diagnosis was established on the basis of clinical features and by detection of Pneumocystis carinii cysts in bronchoalveolar lavage fluid. Underlying diseases comprised hematologic malignancies (n=60; 58%), inflammatory diseases (n=27; 26%), and solid tumors (n=18; 17.5%); 9 (8%) patients were solid organ transplant recipients. Seventy-one (69%) patients received cytotoxic drugs, 57 (55%) were treated with long-term corticotherapy, and 15 (14.7%) underwent bone marrow transplantation. Fifty-eight (56%) patients were admitted to the intensive care unit, and 52 (41%) required mechanical ventilation. Thirty-nine (38%) patients died of PCP; data from these patients were compared with those from surviving patients. The following factors were associated with a poor prognosis: high respiratory rate (P=0.005), high pulse rate (P=0.0003), elevated C-reactive protein (P=0.01), elevated serum lactate dehydrogenase level (P=0.02), and mechanical ventilation (OR, 14.4; 95%CI, 5-50). The results suggest that PCP can occur during the course of many immunosuppressive diseases, particularly various hematologic malignancies. The diagnosis of PCP should be considered more frequently and advocated earlier in immunocompromised HIV-negative patients, since prompt diagnosis may improve the prognosis of these patients.

Adolescent↗

Quantitative determination of the spatial distribution of pure- and mixed-strain immobilized cells in gel beads by immunofluorescence.

A new method was developed to detect and quantify two strains, Lactococcus lactis subsp. lactis biovar. diacetylactis MD and Bifidobacterium longum ATCC 15707, immobilized separately and co-immobilized in gel beads, using specific polyclonal antibodies and confocal laser-scanning microscopy. The establishment of biomass concentration profiles for each strain was measured during colonization of beads using successive pH-controlled batch fermentations. Growth occurred preferentially in 200- and 300-microm peripheral layers of the beads for L. diacetylactis and B. longum, respectively. Repeated-batch cultures with immobilized cells permitted the production of a mixed culture containing a non-competitive strain of bifidobacteria, as a result of immobilized-cell growth and high cell-release activity from the beads. During co-immobilized fermentations, there were no apparent interactions between the strains.

Bifidobacterium↗

Tinea pedis in European marathon runners.

BACKGROUND: Epidemiological studies suggest that 15% of the population in industrial countries suffer from tinea pedis (athlete's foot) and that persons who do sports are a high-risk population. OBJECTIVE: To investigate the responsibility of dermatophytes in interdigital lesions of the feet in European marathon runners and to identify associated risk factors. SUBJECTS AND METHODS: Runners of the 14th Médoc Marathon (n = 147) were interviewed on risk factors for tinea pedis and underwent physical and mycological examinations. RESULTS: Interdigital lesions of the feet were found in 66 runners (45%). A dermatophyte was isolated in 45 runners (31%), 12 of whom were asymptomatic. Trichophyton interdigitale and T. rubrum accounted for 49% and 35.5%, respectively, of the cases of tinea pedis. Thirty-three (22%) of the 102 runners free of dermatophyte infection had lesions resembling those of tinea pedis. Increasing age and use of communal bathing facilities were predictive of T. rubrum culture. CONCLUSIONS: Marathon runners are at high risk for tinea pedis, but dermatophytes are responsible for only half of the foot lesions found in runners. The existence of asymptomatic carriers calls for prophylactic measures.

Adult↗

Inflammatory myositis associated with anti-U1-small nuclear ribonucleoprotein antibodies: a subset of myositis associated with a favourable outcome.

OBJECTIVES: Inflammatory myositides are rare chronic disorders which may be either isolated or associated with other conditions such as connective tissue diseases or neoplasia. A large variety of autoantibodies can be detected in patients with myositis, some of which have a diagnostic and/or a prognostic value. Myositis associated with anti-U1-small nuclear ribonucleoprotein antibodies (anti-U1-snRNP Abs) are usually considered as overlapping syndromes, mainly mixed connective tissue diseases (MCTD) in which muscle symptoms occur insidiously during the disease course and are characterized by a favourable outcome. METHODS: The clinical, biological, immunological and pathological findings as well as the outcome of five patients with anti-U1-snRNP-associated myositis were retrospectively analysed. RESULTS: Patients were mainly black females. In all five patients, myositis was the predominant manifestation at presentation. Associated conditions consisted of interstitial lung disease (ILD) (three), arthritis (three) and neurological symptoms (two). No patient presented Raynaud's phenomenon nor met criteria for MCTD. Biological inflammatory features, rheumatoid factor and polyclonal hypergammaglobulinaemia were present in all cases. Besides anti-U1-snRNP Abs, one patient had anti-Ro/SSA and anti-La/SSB Abs at presentation and one additional patient developed anti-double-stranded-DNA and anti-Sm Abs after a follow-up of more than 4 yr. No patient had anti-PM/sclerosis (Scl) nor anti-aminoacyl-tRNA synthetase Abs. All patients dramatically improved with steroids, and reached complete remission (CR) within 3 weeks. Two patients relapsed 18 months after CR. They both reached rapidly second CR using steroids associated or not with oral methotrexate. CONCLUSION: Our data suggest that anti-U1-snRNP Abs may define a subset of myositis characterized by a favourable outcome, though often associated with ILD and/or neurological manifestations.

Adult↗

Antibacterial activities of nisin Z encapsulated in liposomes or produced in situ by mixed culture during cheddar cheese ripening.

This study investigated both the activity of nisin Z, either encapsulated in liposomes or produced in situ by a mixed starter, against Listeria innocua, Lactococcus spp., and Lactobacillus casei subsp. casei and the distribution of nisin Z in a Cheddar cheese matrix. Nisin Z molecules were visualized using gold-labeled anti-nisin Z monoclonal antibodies and transmission electron microscopy (immune-TEM). Experimental Cheddar cheeses were made using a nisinogenic mixed starter culture, containing Lactococcus lactis subsp. lactis biovar diacetylactis UL 719 as the nisin producer and two nisin-tolerant lactococcal strains and L. casei subsp. casei as secondary flora, and ripened at 7 degrees C for 6 months. In some trials, L. innocua was added to cheese milk at 10(5) to 10(6) CFU/ml. In 6-month-old cheeses, 90% of the initial activity of encapsulated nisin (280 +/- 14 IU/g) was recovered, in contrast to only 12% for initial nisin activity produced in situ by the nisinogenic starter (300 +/- 15 IU/g). During ripening, immune-TEM observations showed that encapsulated nisin was located mainly at the fat/casein interface and/or embedded in whey pockets while nisin produced by biovar diacetylactis UL 719 was uniformly distributed in the fresh cheese matrix but concentrated in the fat area as the cheeses aged. Cell membrane in lactococci appeared to be the main nisin target, while in L. casei subsp. casei and L. innocua, nisin was more commonly observed in the cytoplasm. Cell wall disruption and digestion and lysis vesicle formation were common observations among strains exposed to nisin. Immune-TEM observations suggest several modes of action for nisin Z, which may be genus and/or species specific and may include intracellular target-specific activity. It was concluded that nisin-containing liposomes can provide a powerful tool to improve nisin stability and availability in the cheese matrix.

Anti-Bacterial Agents↗

Inhibition of Listeria innocua in cheddar cheese by addition of nisin Z in liposomes or by in situ production in mixed culture.

The effect of addition of purified nisin Z in liposomes to cheese milk and of in situ production of nisin Z by Lactococcus lactis subsp. lactis biovar diacetylactis UL719 in the mixed starter on the inhibition of Listeria innocua in cheddar cheese was evaluated during 6 months of ripening. A cheese mixed starter culture containing Lactococcus lactis subsp. lactis biovar diacetylactis UL719 was selected for high-level nisin Z and acid production. Experimental cheddar cheeses were produced on a pilot scale, using the selected starter culture, from milk with added L. innocua (10(5) to 10(6) CFU/ml). Liposomes with purified nisin Z were prepared from proliposome H and added to cheese milk prior to renneting to give a final concentration of 300 IU/g of cheese. The nisin Z-producing strain and nisin Z-containing liposomes did not significantly affect cheese production and gross chemical composition of the cheeses. Immediately after cheese production, 3- and 1.5-log-unit reductions in viable counts of L. innocua were obtained in cheeses with encapsulated nisin and the nisinogenic starter, respectively. After 6 months, cheeses made with encapsulated nisin contained less than 10 CFU of L. innocua per g and 90% of the initial nisin activity, compared with 10(4) CFU/g and only 12% of initial activity in cheeses made with the nisinogenic starter. This study showed that encapsulation of nisin Z in liposomes can provide a powerful tool to improve nisin stability and inhibitory action in the cheese matrix while protecting the cheese starter from the detrimental action of nisin during cheese production.

Cheese↗

Statistical data validation methods for large cheese plant database.

Production data of the cheesemaking process are used to monitor milk fat and protein recoveries in cheese, cheese yield, and composition and eventually to predict these parameters. Due to the large impact of these factors on cheese quality and plant profitability, it is very important to use reliable data for analysis, modeling, and control of the process. This paper tested six methods for detecting erroneous data in industrial cheesemaking databases. The data analyzed came from 4 yr of stirred-curd Cheddar cheese production in an industrial cheesemaking facility, comprising over 10,000 vats. Single vat outliers were detected using a simple statistical criterion of mean +/- 3.6 SD on single variable distributions, Fourier series modeling of seasonal variables (fat, protein, lactose, and total solids in milk, and protein in whey), and the multivariate Mahalanobis outlier analysis. Detection of outlier productions (corresponding to several vats) was done by applying the mean +/- 3.6 SD criterion to variables obtained through calculating the fat mass balance, fat retention coefficient, and yield efficiency. Data treatment enabled the detection of outlier data, but also pinpointed variables with a low reliability (manually registered times). Single variable and multivariable methods proved complementary, and the use of both types of methods is recommended when validating an existing database.

Analysis of Variance↗

[Methemoglobinemia induced by repeated abuse of lidocaine viscous gel].

Lidocaine use may lead to methemoglobinemia. Lidocaine is clinically widely used as an anaesthesic drug, however its toxic effect is rare. We report a high methemoglobinemia level of 31.1% following repeated Xylocaine gel oral applications. New metabolic pathways of lidocaine have been reported leading to dimethylphenylhydroxylamine in humans. This metabolism is very similar to the aniline derivative ones, and may explain lidocaine methemoglobinemia effect.

Adult↗

Physicians Taking Action Against Smoking: an intervention program to optimize smoking cessation counselling by Montreal general practitioners.

In 1997 the Direction de la santé publique de Montréal-Centre initiated "Physicians Taking Action Against Smoking," a 5-year intervention program to improve the smoking cessation counselling practices of general practitioners (GPs) in Montreal. Program development was guided by the precede-proceed model. This model advocates identifying factors influencing the outcome, in this case counselling practices. These factors are then used to determine the program objectives, to develop and tailor program activities and to design the evaluation. Program activities during the first 3 years included cessation counselling workshops and conferences for GPs, publication of articles in professional interest journals, publication of clinical guidelines for smoking cessation counselling and dissemination of educational material for both GPs and smokers. The program also supported activities encouraging smokers to ask their GPs to help them stop smoking. Results from 2 cross-sectional surveys, conducted in 1998 and 2000, of random samples of approximately 300 GPs suggest some improvements over time in several counselling practices, including offering counselling to more patients and discussing setting a quit date. More improvements were observed among female than male GPs in both psychosocial factors related to counselling and specific counselling practices. For example, improvements were noted among female GPs in self-perceived ability to provide effective counselling and in the belief that it is important to schedule specific appointments to help patients quit; in addition, the perceived importance of several barriers to counselling decreased among female GPs. A greater proportion of the female respondents to the 2000 survey offered written educational material than was the case in 1998, and a greater proportion of the male GPs devoted more time to counselling in 2000 than in 1998; however, among male GPs the proportion who discussed the pros and cons of smoking with patients in the pre-contemplation stage declined between 1998 and 2000, as did the proportion who referred patients in the preparation stage to community resources. Our experience suggests that an integrated, theory-based program to improve physicians' counselling practices could be a key component of a comprehensive strategy to reduce tobacco use.

Counseling↗

Role of CD23 in astrocytes inflammatory reaction during HIV-1 related encephalitis.

Soluble factors released by intra-cerebral activated cells are implicated in neuronal alterations during central nervous system inflammatory diseases. In this study, the role of the CD23 pathway in astrocyte activation and its participation in human immunodeficiency virus-1 (HIV-1)-induced neuropathology were evaluated. In human primary astrocytes, CD23 protein membrane expression was dose-dependently upregulated by gp120. It was also upregulated by gamma-interferon (gamma-IFN) and modulated by interleukin-1-beta (IL-1beta) whereas microglial cells in these stimulation conditions did not express CD23. Cell surface stimulation of CD23 expressed by astrocytes induced production of nitric oxide (NO) and IL-1beta which was inhibited by a specific inducible NO-synthase (iNOS) inhibitor (aminoguanidine), indicating the implication of this receptor in the astrocyte inflammatory reaction. On brain tissues from five out of five patients with HIV-1-related encephalitis, CD23 was expressed by astrocytes and by some microglial cells, whereas it was not detectable on brain tissue from five of five HIV-1-infected patients without central nervous system (CNS) disease or from two of two control subjects. In addition, CD23 antigen was co-localized with iNOS and nitrotyrosine on brain tissue from patients with HIV1-related encephalitis, suggesting that CD23 participates in iNOS activation of astrocytes in vivo. In conclusion, CD23 ligation is an alternative pathway in the induction of inflammatory product synthesis by astrocytes and participates in CNS inflammation.

AIDS Dementia Complex↗

[Epidemiology of tinea capitis].

PREDOMINANT IN CHILDREN: Tinea capitis is the most frequent fungal infection in children under the age of puberty. It occurs only rarely in men but is observed in adult women. Human-to-human, animal-to-human and soil-to-human transmission can be involved. HISTORICAL BACKGROUND: The spectrum of fungal species known to cause tinea capitis has steadily grown for more than a century, varying with the local urban or rural environment. Since the beginning of the 20th century and up to the advent of griseofulvin in the sixties, M. audouinii, an anthropophilic species, caused major epidemics in France, England and the USA. In the sixties to eighties, M. canis was the cause of most cases observed throughout the world. Over the last 20 years, anthropophilic species have again become the leading cause of tinea capitis epidemics, particularly in large cities, in relationship with immigration: T. tonsuransi in the USA and England and T. soudanense and M. langeronii in France. HYGIENE AND EDUCATION: Despite the benign curable nature of the disease, interhuman transmission of tinea capitis is nevertheless a considerable public health problem due to the increasing number of children affected and the risk of contagion in schools. The considerations resulting from recent studies point out the fact that transmission occurs more often in the family than the school setting, particularly indirectly by common use of grooming instruments. This would explain the high percentage of tinea capitis in large immigrant families where hair combing habits favor transmission. In France, these observations should lead to a revision of the current regulations concerning expulsion from school of children affected by tinea capitis. Better education would be a more appropriate response to the problem.

Adolescent↗

Massive gene decay in the leprosy bacillus.

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.

Animals↗