Salmonella enterica serovar Typhimurium is a primary enteric pathogen infecting both humans and animals. Infection begins with the ingestion of contaminated food or water so that salmonellae reach the intestinal epithelium and trigger... more
Salmonella enterica serovar Typhimurium is a primary enteric
pathogen infecting both humans and animals. Infection begins
with the ingestion of contaminated food or water so that salmonellae
reach the intestinal epithelium and trigger gastrointestinal
disease. In some patients the infection spreads upon invasion of
the intestinal epithelium, internalization within phagocytes, and
subsequent dissemination. In that case, antimicrobial therapy,
based on fluoroquinolones and expanded-spectrum cephalosporins
as the current drugs of choice, is indicated. To accomplish the
pathogenic process, the Salmonella chromosome comprises several
virulence mechanisms. The most important virulence genes
are those located within the so-called Salmonella pathogenicity
islands (SPIs). Thus far, five SPIs have been reported to have a
major contribution to pathogenesis. Nonetheless, further virulence
traits, such as the pSLT virulence plasmid, adhesins, flagella,
and biofilm-related proteins, also contribute to success within the
host. Several regulatory mechanisms which synchronize all these
elements in order to guarantee bacterial survival have been described.
These mechanisms govern the transitions from the different
pathogenic stages and drive the pathogen to achieve maximal
efficiency inside the host. This review focuses primarily on the
virulence armamentarium of this pathogen and the extremely
complicated regulatory network controlling its success.
pathogen infecting both humans and animals. Infection begins
with the ingestion of contaminated food or water so that salmonellae
reach the intestinal epithelium and trigger gastrointestinal
disease. In some patients the infection spreads upon invasion of
the intestinal epithelium, internalization within phagocytes, and
subsequent dissemination. In that case, antimicrobial therapy,
based on fluoroquinolones and expanded-spectrum cephalosporins
as the current drugs of choice, is indicated. To accomplish the
pathogenic process, the Salmonella chromosome comprises several
virulence mechanisms. The most important virulence genes
are those located within the so-called Salmonella pathogenicity
islands (SPIs). Thus far, five SPIs have been reported to have a
major contribution to pathogenesis. Nonetheless, further virulence
traits, such as the pSLT virulence plasmid, adhesins, flagella,
and biofilm-related proteins, also contribute to success within the
host. Several regulatory mechanisms which synchronize all these
elements in order to guarantee bacterial survival have been described.
These mechanisms govern the transitions from the different
pathogenic stages and drive the pathogen to achieve maximal
efficiency inside the host. This review focuses primarily on the
virulence armamentarium of this pathogen and the extremely
complicated regulatory network controlling its success.
Objectives: To investigate the potential relationship between quinolone resistance and biofilm production in a collection of Salmonella enterica clinical isolates and in S. enterica serovar Typhimurium serial mutants with increasing... more
Objectives: To investigate the potential relationship between quinolone resistance and biofilm production in a collection of Salmonella enterica clinical isolates and in S. enterica serovar Typhimurium serial mutants with increasing resistance to ciprofloxacin. Methods: Nalidixic acid susceptibility and biofilm formation were assessed in a collection of 122 S. enterica clinical isolates. An in vitro quinolone-resistant mutant, 59-64, was obtained from a biofilm-producing and quinolone-susceptible clinical isolate, 59-wt, in a multistep selection process after increasing ciprofloxacin concentrations. The quinolone resistance mechanisms [target gene and multidrug resistance (MDR) regulatory mutations, MICs of several antibiotics, cell envelope protein analysis, real-time PCR and ciprofloxacin accumulation] were characterized for mutant strains. In addition, analysis of fitness, biofilm formation, rdar morphotype and expression of biofilm-related genes by real-time PCR were also determined. Results: Nalidixic acid-susceptible S. enterica strains were more prevalent in producing biofilm than the resistant counterparts. Strain 59-64 acquired five target gene mutations and showed an MDR phenotype. AcrAB and acrF overexpression were ruled out, whereas TolC did show increased expression in 59-64, which, in addition, accumulated less ciprofloxacin. Consistently, increased ramA expression was seen in 59-64 and attributed to a mutation within its promoter. Reduced biofilm production related to diminished csgB expression as well as reduced fitness was seen for 59-64, which was unable to form the rdar morphotype. Conclusions: Quinolone resistance acquisition may be associated with decreased production of biofilm due to lower csgB expression. Efflux, biofilm production and fitness seem to be interrelated.
The aim of this study was to investigate the prevalence of extended-spectrum b-lactamase (ESBL)-producing Escherichia coli in stool samples from 457 patients with travellers' diarrhoea who had travelled to tropical and subtropical... more
The aim of this study was to investigate the prevalence of extended-spectrum b-lactamase (ESBL)-producing Escherichia coli in stool samples from 457 patients with travellers' diarrhoea who had travelled to tropical and subtropical countries. Ninety-seven ESBL-producing E. coli strains were isolated from 17.9% of the patients (82/457). CTX-M-15 was the most prevalent enzyme (80%) and India was the most visited country and showed the highest prevalence of positive samples (37.4%).
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Información del artículo Tratamiento de la infección aguda de la artroplastia total o parcial de cadera con desbridamiento y régimen antibiótico oral.
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SoxS, MarA, and Rob are homologous transcriptional activators of numerous superoxide- and antibiotic resistance genes but many of the regulated genes are yet to be characterized. In this study, microarrays and RT-PCR analysis were used to... more
SoxS, MarA, and Rob are homologous transcriptional activators of numerous superoxide- and antibiotic resistance genes but many of the regulated genes are yet to be characterized. In this study, microarrays and RT-PCR analysis were used to show the overexpression of the ompN porin and its upstream gene, ydbK, in an Escherichia coli multidrug-resistant mutant and in a strain constitutive for SoxS. However, transcriptional fusions revealed that SoxS (not MarA or Rob) only activated the ydbK promoter but not the ompN upstream region. RT-PCR experiments showed the overexpression of a combined ydbK - ompN transcript in the SoxS-overexpressing strain. Surprisingly, a bioinformatic approach revealed no soxbox upstream of the ydbK promoter. Thus, the ydbK and ompN genes are coexpressed in an operon and are likely activated by SoxS indirectly. It is known that YdbK is involved in superoxide resistance. Thus, individual ompN and ydbK mutants were tested for superoxide susceptibility. Nonetheless, only the ydbK mutant was susceptible to paraquat, a superoxide generator. These mutants, as well as an OmpN-overproducing strain, were further tested for antibiotic resistance. No significant decreased susceptibility was observed. Thus, ydbK plays a role in superoxide resistance but no role for either gene is found in resistance to the antibiotics tested.
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Research Interests: Survival Analysis, Gene expression, Spain, Biological Sciences, Disease Outbreaks, and 16 moreHumans, Female, Male, Aged, Middle Aged, Anti-Bacterial Agents, Adult, Colistin, Carbapenems, Microbial Sensitivity Tests, Acinetobacter baumannii, Minocycline, Cross-infection, Acinetobacter Infections, Beta Lactamases, and microbial drug resistance
One hundred and twenty three strains of Shigella spp. (mostly Shigella sonnei and Shigella flexneri) were isolated between 1995 and 2000 from patients suffering from traveller's diarrhoea. Seventy nine of them have been typed by... more
One hundred and twenty three strains of Shigella spp. (mostly Shigella sonnei and Shigella flexneri) were isolated between 1995 and 2000 from patients suffering from traveller's diarrhoea. Seventy nine of them have been typed by digestion of their chromosomal DNA with Xba I and pulsed field gel electrophoresis. Results show a high degree of heterogeneity in both S. sonnei and S. flexneri isolates. This is the first time that the molecular typing of such a high number of geographically unrelated isolates of Shigella sp. is carried out, showing a high level of genomic re-arrangement.
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Background: Bloodstream infections are a significant cause of neonatal morbidity and death. An increase in the incidence of early neonatal sepsis due to Escherichia coli has been reported. The objective was to evaluate the antimicrobial... more
Background: Bloodstream infections are a significant cause of neonatal morbidity and death. An increase in the incidence of early neonatal sepsis due to Escherichia coli has been reported. The objective was to evaluate the antimicrobial resistance of E. coli strains causing early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS) and their evolution. Methods:E. coli strains from EONS and hospital-acquired
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ABSTRACT In this review we have tried to present a complete and integrated picture of the old and new ways to discover antibacterial agents. The development of new antibacterial agents can be made from derivatives of known antibacterial... more
ABSTRACT In this review we have tried to present a complete and integrated picture of the old and new ways to discover antibacterial agents. The development of new antibacterial agents can be made from derivatives of known antibacterial agents or by identification of novel agents active against previously unexploited targets. The genetic and biochemical basis of resistance to most classes of antibacterial agents is now known and this has been important in the design of a rational strategy that can be used to counteract resistance. This strategy can follow two approaches: i. Modification of the basic structure of the antibacterial agent, which circumvents antibacterial resistant mechanisms, and ii. Development of a compound inhibiting the mechanism of resistance for an antibacterial agent, hence the concomitant administration of the antibacterial agent plus the inhibitor, as a co-drug, will potentiate this activity. There are also two main approaches to find new protein targets: 1. Classical and, 2. Genomic. The first includes the study of secondary metabolites of bacteria and fungi with antibacterial activity, and it has now been expanded to include plant extracts and marine macro- and microorganisms, as well as non-cultivable soil bacteria. Recent tools such as comparative genomic, combinatorial chemistry, and computerized modelling have helped in the development of new antibacterial agents. Finally, other approaches, such as bacteriophages, antisense RNA and proteins involved in pathogenicity to find new antibacterial drugs are currently investigated.
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Antibiotic resistance in clinical isolates of Salmonella typhimurium has steadily risen in recent years. Some of the resistance genes may be carried into integrons. In this study, integrons, both from 10 epidemiologically related and... more
Antibiotic resistance in clinical isolates of Salmonella typhimurium has steadily risen in recent years. Some of the resistance genes may be carried into integrons. In this study, integrons, both from 10 epidemiologically related and unrelated S. typhimurium clinical isolates, were characterized, showing that epidemiologically different strains can carry the same integron, and that epidemiologically related strain can carry different integrons. Among the resistance genes detected in this study were genes encoding b-lactamases (bla(oxa-30) in two strains, and bla(pse-1) in five strains, one of which was carrying this cassette in two different integrons); aminoglycoside-modifying enzymes (aadA2 in four strains, one of which was carrying this cassette in two different integrons, and aadA1 in six strains); as well dihydrofolate reductases (dfrAI in three strains).
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Adherence of microorganisms to a surface is the first step in the formation of most biofilms. Adherence can take place on both virgin material and material coated with proteins or glycoproteins generated by the host. The importance of... more
Adherence of microorganisms to a surface is the first step in the formation of most biofilms. Adherence can take place on both virgin material and material coated with proteins or glycoproteins generated by the host. The importance of these mechanisms depends on the type of implant. In this review we will discuss the molecular basis of bacterial adherence to inert material, the implication of adherence in biofilm formation, and the advantages of biofilm production by bacteria causing prosthesis-associated infection.
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To analyze the usefulness of D-lactic acid levels in synovial fluid (SF) as a rapid test to support the early diagnosis of bacterial arthritis (BA). A simple modification of the enzyme method used for measuring L-lactic acid was used to... more
To analyze the usefulness of D-lactic acid levels in synovial fluid (SF) as a rapid test to support the early diagnosis of bacterial arthritis (BA). A simple modification of the enzyme method used for measuring L-lactic acid was used to analyze levels of D-lactic acid in SF from 20 cases of BA. Results were compared with those from 99 noninfectious arthritis, which included 90 inflammatory SF samples. Total white blood cell count (WBC), percentage of polymorphonuclears (% PMN) and gram stains were also determined. D-lactic acid levels were significantly higher in BA than in noninfectious arthritis. Using a cutoff value of 0.05 mM, 85% of the SF samples from BA had a positive test for D-lactic acid compared with 4% of the control group. The overall sensitivity of the assay was 85% with a specificity of 96%, showing a positive predictive value for BA of 81% and a negative predictive value of 97%. The data presented suggest that D-lactic acid is an accurate, easy test that can be carried out in any laboratory, to support the early diagnosis of BA.
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New virulence factors associated with the genus Shigella have been described recently. These comprise enterotoxins ShET-1 and ShET-2, encoded by the set and sen genes, respectively, and the secreted autotransporter toxin Sat, encoded by... more
New virulence factors associated with the genus Shigella have been described recently. These comprise enterotoxins ShET-1 and ShET-2, encoded by the set and sen genes, respectively, and the secreted autotransporter toxin Sat, encoded by the sat gene. The present study aimed to determine the prevalence of genes encoding these toxins among a collection of Shigella flexneri clinical isolates belonging to different serotypes. While the set gene was detected only in S. flexneri serotypes 2a and 2b, the sen and sat genes were present in diverse serotypes of S. flexneri.
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Although the clinical importance of Acinetobacter pittii and Acinetobacter nosocomialis has increased in the nosocomial setting in the last decade, infections caused by Acinetobacter baumannii still have the highest clinical relevance.... more
Although the clinical importance of Acinetobacter pittii and Acinetobacter nosocomialis has increased in the nosocomial setting in the last decade, infections caused by Acinetobacter baumannii still have the highest clinical relevance. The most important features of this latter species are the ability to persist in the hospital environment and the multi-drug, extended-drug or pandrug resistance they may present which compromises the treatment of infections caused by this microorganism. In the present review, the authors describe the molecular bases of the acquisition of resistant mechanisms as well as different current and potential future strategies to treat infections caused by multi-drug resistant A. baumannii. With the increase in resistance to carbapenems, colistin has been extensively used, however some data suggest that the doses recommended are insufficient before a steady state is reached, suggesting that the administration of a loading dose on initiation of treatment may be beneficial. Combinations of antibacterial agents such as impenem plus sulbactam or imipenem plus colistin have been successfully used to treat VAP. Nonetheless, future alternatives for treating A. baumannii infections should be explored.
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The prevalence and characterization of Class 1 integrons has been performed in eighty three strains of Shigella spp., isolated between 1995 and 2000 from patients with traveler's diarrhea. A low prevalence (13.25%) was recorded.... more
The prevalence and characterization of Class 1 integrons has been performed in eighty three strains of Shigella spp., isolated between 1995 and 2000 from patients with traveler's diarrhea. A low prevalence (13.25%) was recorded. Nine different integrons were found among 11 multiresistant strains, with a total of 10 different gene cassettes encoding for resistance to trimethoprim (dfrA1, dfrA5, dfrA7, dfrA12, and dfrA15), aminoglycosides (aadA1a and aadA2), beta-lactam antibiotics (oxa2) or ORF with unknown function (orfD and orfF). A high prevalence of dfr and aad gene cassettes was observed. The low incidence of Class 1 integrons observed in this study is in contrast with the known facility that the Shigella genus has to gain and transfer plasmids.
Research Interests: Genetics, Microbiology, Molecular Biology, Medical Microbiology, Spain, and 12 moreTravel, Humans, Polymerase Chain Reaction, Clinical Sciences, Integrons, Anti-Bacterial Agents, Molecular Characterization, Microbial Sensitivity Tests, Base Sequence, Sensitivity and Specificity, Shigella, and Molecular Sequence Data
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Among non-fermenting Gram-negative rods, the most clinically important species are Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia, which are frequently multiresistant. P. aeruginosa resistance to... more
Among non-fermenting Gram-negative rods, the most clinically important species are Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia, which are frequently multiresistant. P. aeruginosa resistance to beta-lactams depends on the production of chromosomal and plasmid-mediated beta-lactamases, altered permeability (loss of OprD porin is related to carbapenem-resistance) and active efflux pumps, particularly MexAB-OprM. In aminoglycoside-resistant strains the main mechanism of resistance is the production of inactivating enzymes; the efflux pump MexXY-OprM is also involved. Quinolone-resistance in P. aeruginosa is related to changes in topoisomerases, altered permeability and efflux pumps. The mechanisms of resistance of A. baumannii have not been well characterized, which makes interpretative reading of the antibiogram in this organism difficult. Resistance to beta-lactams is associated with the production of beta-lactamases and altered penicillin-binding proteins. Resistance to aminoglycosides has been related to modifying enzymes and resistance to quinolones to altered targets. S. maltophilia is resistant to carbapenems and other beta-lactams because of the production of two beta-lactamases (L-1 and L-2). Aminoglycoside-modifying enzymes have also been described in this species. In contrast to what is observed in other organisms, S. maltophilia resistance to quinolones has been mainly related to active efflux, rather than to target alterations.
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Acinetobacter baumannii are non-fermentative, Gram-negative bacilli that cause a large number of nosocomial infections worldwide. They are characterized by frequent multiresistance due to multiple mechanisms. As a consequence, infections... more
Acinetobacter baumannii are non-fermentative, Gram-negative bacilli that cause a large number of nosocomial infections worldwide. They are characterized by frequent multiresistance due to multiple mechanisms. As a consequence, infections caused by strains exhibiting resistance to carbapenems and, sometimes, polymyxins, are regularly observed. Sulbactam, colistin and combinations of different antimicrobials have been reported as new therapeutic approaches for infections caused by resistant A baumannii strains. This review focuses on current and potential new drugs, such as rifampin, tigecycline, antimicrobial peptides, efflux pump resistant and inhibitor drugs, and enzyme inhibitors.