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Carbon metabolic homogenization is linked to microbial competition and antimicrobial resistance in soils under forest-to-cropland conversion.

Global agricultural expansion by converting natural forests into croplands often leads to soil functional homogenization and antimicrobial resistance enhancement, threatening ecosystem services. However, the associations between microbial carbon metabolic homogenization and antimicrobial resistance remain largely unknown. Here, we collected 240 paired forest and cropland soil samples from the most intensively farmed Yangtze River Basin in China, and constructed a novel framework based on microbial functional traits to decipher the role of carbon metabolic homogenization on antimicrobial resistance via microbial competition for metabolites. Using genome-scale metabolic models, we found that carbon metabolic homogenization was associated with a shift in microbial interactions from cooperation toward competition, with a 45.6% increase in competitive interactions that coincided with a 35.6% higher antimicrobial resistance gene (ARG) diversity. This shift was accompanied by smaller genome sizes and higher 16S rRNA copy numbers, indicating fast-growing, resource-acquisitive microbial strategies. Metabolic transfer analyses further revealed less cooperation relationships among microbial communities in cropland soils than in forest soils, indicating an intensified battle for communal metabolites and an attenuated exchange for complementary metabolites. Together, these findings provide a new framework to understand the association between carbon metabolic homogenization and soil antimicrobial resistance risks from the perspective of microbial traits and interactions under land use change.

Soil Microbiology↗

Nucleotide-binding oligomerization domain-like receptors: intracellular pattern recognition molecules for pathogen detection and host defense.

The nucleotide binding oligomerization domain-like receptor (NLR) family of pattern recognition molecules is involved in a diverse array of processes required for host immune responses against invading pathogens. Unlike TLRs that mediate extracellular recognition of microbes, several NLRs sense pathogens in the cytosol and upon activation induce host defense signaling pathways. Although TLRs and NLRs differ in their mode of pathogen recognition and function, they share similar domains for microbial sensing and cooperate to elicit immune responses against the pathogen. Genetic variation in several NLR genes is associated with the development of inflammatory disorders or increased susceptibility to microbial infection. Further understanding of NLRs should provide critical insight into the mechanisms of host defense and the pathogenesis of inflammatory diseases.

Adaptor Proteins, Signal Transducing↗

Trends in the activity of macrolide and beta-lactam antibiotics and resistance development. Alexander Project Group.

The Alexander Project is an ongoing international multicenter study monitoring trends in the antimicrobial susceptibilities of community-acquired lower respiratory tract (LRT) pathogens. In 1995, 4011 isolates were collected. The incidence of beta-lactamase-positive Haemophilus influenzae was 28.4% in the United States and 15.4% in Europe, and the incidence of beta-lactamase-positive Moraxella catarrhalis has risen to > 90% in Europe and the United States. The incidence of penicillin-resistant Streptococcus pneumoniae is higher in Europe (24.9%) than the Unites States (12.3%). For the majority of centers, there is a marked association between penicillin and macrolide resistance in S. pneumoniae with erythromycin, azithromycin and clarithromycin exhibiting MIC90s of > or = 32 mg/l against penicillin-resistant strains. For Toulouse and Genoa, at least, the high levels of macrolide resistance may be attributable to high macrolide usage. Ceftriaxone and amoxycillin/clavulanate are the most potent agents for empirical therapy, with MIC90s of < or = 2 mg/l against all three principal pathogens. The majority of oral agents studied are active against > 90% H. influenzae and M. catarrhalis and > 80% S. pneumoniae on breakpoint criteria. However, on the basis of the time above MIC criteria for the beta-lactam and macrolide agents tested, only amoxycillin/clavulanate and the parenteral agent ceftriaxone can be recommended for empirical therapy of LRT infections caused by these pathogens.

Anti-Bacterial Agents↗

Epilithic biofilms in Saint Callixtus Catacombs (Rome) harbour a broad spectrum of Acidobacteria.

The phylum Acidobacteria is broadly represented in a variety of environments as reported during microbial molecular surveys. This study represents the first attempt to analyze the diversity of Acidobacteria in Roman Catacombs (Rome, Italy). Both 16S and 23S rRNA gene sequences were used to confirm the affiliation within different acidobacterial subgroups. The results showed Acidobacteria belonging to subgroups 3, 4, 6, 9, and 10 in the analyzed samples. The presence of acidobacterial sequences in biodeteriorating biofilms in Roman Catacombs suggest they could participate in this negative process, most likely in cooperation with other microbial groups.

Bacteria↗

[Ecological interpretation and related strategies for low culturability of microorganisms].

Pure culture technique has been a fundamental method since its invention in microbiology, but its isolated and monotonous environment contradicts microbial diversity and cooperation relationship in natural environment. And this contradiction directly results in the uncultivability of some microbes in media. From ecological viewpoint, the recovery barriers of natural microbes mainly include the crash of cooperation in natural environment, the great change of nutrient in new environment and the loss of native niche. The main methods and strategies on low curturability of microorganisms are culture-independent methods, enrichment culture, mixed culture, dilution culture, simulating nature culture and synthetic method, which can to some degree compensate for the traditional approach and improve the low culturability of some bacteria.

Biodiversity↗

Ultrastructural features of microbial colony organization.

The ultrastructure of microbial colonies was studied. Inside the colonies three types of intercellular contacts were demonstrated. In the colonies of Gram-negative bacteria, the cells were found to be connected by tight adhesions of outer membranes of the cell walls and membrane bridges. In the colonies of Gram-positive bacteria, the intercellular contacts were formed by fusion of peptidoglucan layers of the cell walls. Bacterial cells were differentiated by the presence of a capsule-like envelope. The obtained data indicate the existence of elements of cellular cooperation and specialization in microbial colonies.

Bacterial Adhesion↗

Delvotest SP for detection of cloxacillin and sulfamethoxazole in milk: IDF interlaboratory study. International Federation Dairy.

Under the auspices of the International Dairy Federation's Group E503, a collaborative study of the Delvotest SP multiplate microbial inhibitor test was performed to gain information about the detection limits of 2 antimicrobial agents (a beta-lactam and a sulfa compound), the variation of test results between users and 2 batches of the test, and the reasons for deviating results. Lyophilized milk samples spiked with various concentrations of cloxacillin or sulfamethoxazole were analyzed. Each substance/concentration combination was tested with each of 2 test batches 14 or 15 times per participating laboratory. Test results were to be read by more than one person and reported on separate forms. Results were obtained from 29 laboratories, which included 5 with no experience and 11 with limited experience with this test. Detection limits for cloxacillin (22.5 or 30 micrograms/kg, depending on batch) and sulfamethoxazole (45 micrograms/kg) were established from dose-response curves. A small difference in cloxacillin detection levels between the 2 test batches was observed. Analyses of samples gave almost unanimous results (> or = 95%). Of deviating results, defined as anomalous results (1.4% of readings), half could be attributed to human errors and half to procedural errors.

Animals↗

Comparative activity of oral and parenteral cephalosporins tested against multidrug-resistant Streptococcus pneumoniae: report from the SENTRY Antimicrobial Surveillance Program (1997-2003).

A large international collection of Streptococcus pneumoniae (21605 strains) was analyzed to determine the comparative activity of selected oral (cefuroxime and cefpodoxime) and parenteral (ceftriaxone and cefepime) cephalosporins when tested against different antimicrobial resistance phenotypes including penicillin-resistant strains and strains displaying additional resistances to other agents (erythromycin, clindamycin, tetracycline, and trimethoprim/sulfamethoxazole). The multidrug-resistant (MDR) rate ranged from 17.6% (penicillin- and erythromycin-resistant only) to 5.7% (resistance to all 5 drugs). The parenteral cephalosporins retained wider activity for all MDR phenotypes studied with the resistance rates (minimum inhibitory concentration > or = 4 mug/mL) being lower for cefepime (1.3-1.9%) when compared with ceftriaxone (3.0-4.4%) or the orally administered cephalosporins, cefpodoxime (64.4-74.1%), and cefuroxime (69.3-79.1%). Our findings confirm that the parenteral cephalosporins, cefepime, and ceftriaxone possess significant activity against those MDR pneumococci responsible for an increasing number of serious respiratory tract infections.

Administration, Oral↗

Spoligotyping and IS6110-RFLP typing of Mycobacterium tuberculosis from French Guiana: a comparison of results with international databases underlines interregional transmission from neighboring countries.

In this investigation, 94 clinical isolates of Mycobacterium tuberculosis obtained over a 3-year period (1996-1998) from French Guiana were characterized by spoligotyping and IS6110-RFLP and the patterns obtained were compared with genotypes representing the worldwide diversity in an international spoligotyping database (n = 4269) and a IS6110-RFLP database (n = 4189). All the clustered isolates giving < or = 6 copies of IS6110 were further typed using the double-repetitive element (DRE)-PCR. The results obtained underlined the highly diverse nature of the M. tuberculosis population in French Guiana with potential links to neighboring countries within the Americas. It may be hypothesized that the genetic heterogeneity of tubercle bacilli in French Guiana is linked to the high number of imported cases of tuberculosis, that may account for as high as 68% of all tuberculosis cases. Although an epidemiological investigation based on direct interrogation of patients was not performed, available medical records suggested that the clustering of isolates was mostly linked to the following risk factors: pulmonary tuberculosis, smear-positive samples, foreign-born nationals and/or immigrants, and a high rate of HIV-TB coinfection. Thus the persisting foci of endemic disease and increased active transmission due to high population flux and HIV coinfection may be largely responsible for the relatively high incidence of tuberculosis in French Guiana.

Adult↗

DOTS-Plus for multidrug-resistant tuberculosis in the Philippines: global assistance urgently needed.

SETTING: The Philippines, a high burden country for tuberculosis (TB). STUDY DESIGN: Health Operational Study. OBJECTIVE: To describe preliminary data from the Makati Medical Center (MMC)-DOTS Plus pilot project. METHODS: Patients were consecutively enrolled after confirmation of MDR-TB status. Individualized treatment regimens were based on drug susceptibility testing and history of previous intake for the other drugs that were not tested. Treatment outcome in those who had completed at least 18 months of therapy and interim outcome for those who received more than 12 months but less than 18 months were analyzed. RESULTS: One hundred forty-nine patients with MDR-TB were enrolled from April 1999 to 30 May 2002 at the MMC DOTS Clinic. Referrals were from private institutions and practicing physicians in 73.2% of cases. Approximately 30% of isolates tested were resistant to all five first-line drugs, 39.4% to four, 16.8% to three, 12.1% to two. Fluoroquinolone resistance was noted in 40.9% of all the isolates, including 54.5% of those resistant to five drugs and 34.6% of those resistant to four drugs. The outcome of 23 patients who completed therapy and 62 who have received more than 12 months therapy showed cure and likely cure in 73.4% of cases and failure in 3.8% and likely failure in 6.3%. Death occurred in 3.8% and default was observed in 11.4%. CONCLUSION: The MMC DOTS-Plus pilot project is a public-private collaboration in TB Control. Response to therapy was encouraging. Complete subsidy of medicines and laboratory and clinic services and DOT were essential in the successful implementation of the program. DOTS-Plus and DOTS should go hand in hand in TB control if MDR-TB is highly prevalent.

Adolescent↗

Antibiotic resistance in Neisseria gonorrhoeae.

The incidence of gonorrhea is increasing in developed countries and remains high elsewhere. This untenable disease burden, the complication rate in women and newborns, and the amplification of human immunodeficiency virus transmission that accompanies gonorrhea makes control of gonococcal disease a priority. However, antibiotic resistance in Neisseria gonorrhoeae has severely compromised the successful treatment of gonorrhea. Older therapies are ineffective, whereas those that remain efficacious are unaffordable in many high-incidence settings. Penicillins, tetracyclines, and newer macrolides have limited utility, and spectinomycin (and in many parts of the world, quinolones) have been withdrawn because of resistance. Of the usually recommended treatments, only the third-generation cephalosporins, and most notably ceftriaxone, have retained their efficacy, but decreased susceptibility to these antibiotics has also appeared. A sustained decrease in gonococcal disease requires an integrated approach combining improved prevention, better diagnosis, and effective treatment. Without continued commitment and effort, gonorrhea may well become untreatable.

Anti-Bacterial Agents↗

Patterns of multidrug resistance among methicillin-resistant hospital isolates of coagulase-positive and coagulase-negative staphylococci collected in the international multicenter study RESIST in 1997 and 1998.

The primary purpose of the multicenter international study "RESIST" was to obtain an update on the degree of multidrug resistance among methicillin-resistant staphylococci collected from a geographically diverse sample. A total of 3,307 staphylococcal isolates were recovered from single patients and primarily from clinical specimens that were collected at 20 collaborating regional health centers located in several countries in Europe, Asia, and Latin America during a 3- to 4-month period each in 1997 and 1998. All strains were deposited at the Laboratory of Molecular Genetics at ITQB/UNL in Oeiras, Portugal, for quality control and for testing by microbiological and molecular typing techniques; the Laboratory of Microbiology at The Rockefeller University serving as organizational center. The majority of strains, 3,100, were methicillin-resistant, of which 1,749 were coagulase positive (methicillin-resistant Staphylococcus aureus, MRSA), and 1,351 were coagulase negative (methicillin-resistant coagulase negative staphylococci, MRCNS). The overall frequency of drug resistance traits among the 1,749 MRSA strains was high (over 70% and up to and over 90% of the strains) to ciprofloxacin, erythromycin, clindamycin, gentamicin, and tetracycline, and was somewhat less frequent to sulfamethoxazole-trimethoprim (45%), chloramphenicol (30%), and rifampin (38%). None of the 3,307 staphylococcal isolates showed reduced susceptibility to vancomycin except for a single methicillin-resistant coagulase-negative isolate. The great majority of staphylococci were also susceptible to the new antimicrobial Synercid. In contrast, resistance to teicoplanin was significant among methicillin-resistant strains of coagulase-negative staphylococci, particularly among Staphylococcus haemolyticus. MRSA isolates showed marked geographic variation in their patterns of multiresistance, most likely reflecting the properties of unique multiresistant MRSA clones dominant in the hospitals that provided the MRSA isolates from the various geographic areas. The multiresistance patterns of MRSA strains and strains of methicillin-resistant coagulase-negative staphylococci originating at the same country source also showed striking differences, suggesting that resistance to antimicrobial agents emerged under different antibiotic pressures in these bacterial species.

Anti-Bacterial Agents↗

Comparability of antimicrobial susceptibility test results from 22 European countries and Israel: an external quality assurance exercise of the European Antimicrobial Resistance Surveillance System (EARSS) in collaboration with the United Kingdom National External Quality Assurance Scheme (UK NEQAS).

The goal of this exercise was to organize external quality assurance (QA) of antibiotic susceptibility testing for laboratories participating in EARSS and to assess the comparability of susceptibility test results across countries, and guidelines. In September 2000, UK NEQAS distributed a set of three Streptococcus pneumoniae strains, two Staphylococcus aureus strains and one Streptococcus haemolyticus strain. Laboratories reported the guideline followed, the interpretation of the susceptibility test result and the MIC, if tested. In this study we considered results 'concordant' if the reported interpretation of the participating laboratory agreed with the designated interpretation of reference laboratories. Overall, 433 (92%) of 471 laboratories from 23 countries reported back. Of the 8685 tests that were assessed, 8322 (96%) were interpreted correctly by the participants. Concordance for detection of penicillin non-susceptibility in the three S. pneumoniae strains was 96%, 90% and 87%, respectively. Laboratories performed extremely well in detecting oxacillin resistance in the homogeneously methicillin-resistant S. aureus (MRSA) strain, but the concordance rate dropped from 100% to 77% in the heterogeneously resistant MRSA strain. Concordance for detection of teicoplanin resistance in the S. haemolyticus strain was 82%. We stratified concordance rates first for country and then for guideline used, but observed only minor differences among countries and guidelines. Quantitative methods yielding an MIC were more concordant than non-MIC methods for penicillin resistance in the S. pneumoniae strains (94% versus 79%). The NCCLS guideline was the most frequently followed, by 61% of laboratories from 19 countries. This exercise shows that, overall, countries participating in EARSS are capable of delivering susceptibility data of good quality. The comparability of susceptibility data for penicillin resistance in S. pneumoniae and for homogeneous methicillin resistance in S. aureus is satisfactory among European countries and across guidelines. However, we emphasize the importance of determining an MIC for suspected penicillin non-susceptible S. pneumoniae and for suspected glycopeptide non-susceptible S. aureus. Laboratories, particularly in some countries, may need to improve their capability to detect oxacillin resistance in heterogeneously resistant MRSA. For continuous external quality assessment we recommend that laboratories participate in national and international schemes with frequent distribution of control strains.

Drug Resistance, Bacterial↗

Global antibiotic resistance in Streptococcus pneumoniae.

The last two decades of the 20th century were marked by an increasing resistance rate among several bacteria. Threat of resistance is present in Staphylococcus spp., Enterococcus spp., Pseudomonas spp. and Enterobacteriaceae, which are the major pathogens in nosocomial infections. In the community, too, increasing resistance can be observed and is attributed mainly (but not exclusively) to Streptococcus pneumoniae and Haemophilus influenzae. To scrutinize this trend, resistance surveillance in the community was established about 10 years ago. One of the multinational, longitudinal surveillance programmes in place is the Alexander Project, which was established in 1992 to monitor the susceptibility of the major community-acquired lower respiratory tract pathogens to a range of antibacterial drugs. The Alexander Project has revealed a tendency towards increasing resistance of S. pneumoniae to penicillin and macrolide therapy. Within Europe, the prevalence of penicillin resistance among S. pneumoniae isolates is particularly high in France and Spain. Macrolide resistance in S. pneumoniae is also a growing problem in European countries such as France, Spain, Belgium and Italy, where the extent of macrolide resistance in S. pneumoniae now exceeds that of penicillin resistance.

Anti-Bacterial Agents↗