Proteus species bloodstream infections: Comparative epidemiology of three species.

BACKGROUND: Although Proteus species are occasional causes of serious infections, their epidemiology has not been well defined. The objective was to describe the overall and species-specific occurrence and determinants of Proteus species bloodstream infection (BSI) in a large Australian population. METHODS: All Queensland residents with Proteus species BSI identified within the publicly funded healthcare system between 2000 and 2019 were included. RESULTS: A total of 2,143 incident episodes of Proteus species BSI were identified among 2,079 Queensland residents. The prevalence of comorbid illness differed with higher Charlson comorbidity scores observed with P. penneri and P. vulgaris, and higher prevalence of liver disease with P. penneri, higher comorbid cancer with P. vulgaris, and lower diabetes and renal disease prevalence with P. mirabilis BSIs. CONCLUSION: This study provides novel information on the epidemiology of Proteus species BSI.

Copper affects virulence and diverse phenotypes of uropathogenic Proteus mirabilis.

BACKGROUND: Copper plays a role in urinary tract infection (UTI) and urinary copper content is increased during Proteus mirabilis UTI. We therefore investigated the effect of copper on uropathogenic P. mirabilis and the underlying mechanisms, focusing on the virulence associated aspects. METHODS: Mouse colonization, swarming/swimming assays, measurement of cell length, flagellin level and urease activity, adhesion/invasion assay, biofilm formation, killing by macrophages, oxidative stress susceptibility, OMPs analysis, determination of MICs and persister cell formation, RT-PCR and transcriptional reporter assay were performed. RESULTS: We found that copper-supplemented mice were more resistant to be colonized in the urinary tract, together with decreased swarming/swimming, ureases activity, expression of type VI secretion system and adhesion/invasion to urothelial cells and increased killing by macrophages of P. mirabilis at a sublethal copper level. However, bacterial biofilm formation and resistance to oxidative stress were enhanced under the same copper level. Of note, the presence of copper led to increased ciprofloxacin MIC and more persister cell formation against ampicillin. In addition, the presence of copper altered the outer membrane protein profile and triggered expression of RcsB response regulator. For the first time, we unveiled the pleiotropic effects of copper on uropathogenic P. mirabilis, especially for induction of bacterial two-component signaling system regulating fitness and virulence. CONCLUSION: The finding of copper-mediated virulence and fitness reinforced the importance of copper for prevention and therapeutic interventions against P. mirabilis infections. As such, this study could facilitate the copper-based strategies against UTI by P. mirabilis.

Transcriptomic analysis of skin immunity genes in the Chinese spiny frog (Quasipaa spinosa) after Proteus mirabilis infection.

Recently, populations of Chinese spiny frogs (Quasipaa spinosa), an important amphibian species in China, have decreased, mainly due to a disease caused by the gram-negative bacteria Proteus mirabilis. To elucidate the immune response of the frogs, this study aimed to identify novel candidate genes functionally associated with P. mirabilis infection-induced "rotting skin" disease. Chinese spiny frogs were infected with P. mirabilis, and the skin transcriptome was sequenced using the MGISEQ-2000 platform. A total of 233,965 unigenes were obtained by sequencing, of which 27.23 % were known genes. Screening of differentially expressed genes (DEGs) indicated 210 unigenes differentially expressed after P. mirabilis infection, of which 132 unigenes were up-regulated, and 78 unigenes were down-regulated. Using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, DEGs were identified as enriched in signal pathways, such as oxidative phosphorylation, apoptosis, and the Janus kinase-signal transducer and activator of transcription pathway. Of the DEGs, there was a significant upregulation of the colony stimulating factor 2 receptor beta common subunit, interleukin 2 receptor subunit gamma, cathelicidin antimicrobial peptide, interleukin-17 receptor E, receptor-interacting serine/threonine-protein kinase 3, and pulmonary surfactant-associated protein D immune genes following P. mirabilis infection. Conversely, scavenger receptor cysteine-rich domain-containing group B protein, tumor protein p53 inducible nuclear protein 2, suppressor of cytokine signaling 2, and metalloreductase STEAP3 were significantly downregulated. In conclusion, the first skin transcriptome database of Chinese spiny frogs was established, and several immune genes were identified to elucidate the pathogenic mechanism of "skin rot" in Chinese spiny frogs and other cultured frogs.

N-acetylcysteine prevents catheter occlusion and inflammation in catheter associated-urinary tract infections by suppressing urease activity.

Introduction: Proteus mirabilis is a key pathobiont in catheter-associated urinary tract infections (CA-UTIs), which is well known to form crystalline biofilms that occlude catheters. Urease activity alkylates urine through the release of ammonia, consequentially resulting in higher levels of Mg2+ and Ca2+ and formation of crystals. In this study, we showed that N-acetyl cysteine (NAC), a thiol antioxidant, is a potent urease inhibitor that prevents crystalline biofilm formation. Methods: To quantify urease activity, Berthelot's method was done on bacterial extracts treated with NAC. We also used an in vitro catheterised glass bladder model to study the effect of NAC treatment on catheter occlusion and biofilm encrustation in P. mirabilis infections. Inductively-coupled plasma mass spectrometry (ICP-MS) was performed on catheter samples to decipher elemental profiles. Results: NAC inhibits urease activity of clinical P. mirabilis isolates at concentrations as low as 1 mM, independent of bacterial killing. The study also showed that NAC is bacteriostatic on P. mirabilis, and inhibited biofilm formation and catheter occlusion in an in vitro. A significant 4-8log10 reduction in viable bacteria was observed in catheters infected in this model. Additionally, biofilms in NAC treated catheters displayed a depletion of calcium, magnesium, or phosphates (>10 fold reduction), thus confirming the absence of any urease activity in the presence of NAC. Interestingly, we also showed that not only is NAC anti-inflammatory in bladder epithelial cells (BECs), but that it mutes its inflammatory response to urease and P. mirabilis infection by reducing the production of IL-6, IL-8 and IL-1b. Discussion: Using biochemical, microbiological and immunological techniques, this study displays the functionality of NAC in preventing catheter occlusion by inhibiting urease activity. The study also highlights NAC as a strong anti-inflammatory antibiofilm agent that can target both bacterial and host factors in the treatment of CA-UTIs.

Assignment of the antibacterial potential of Ag2O/ZnO nanocomposite against MDR bacteria Proteus mirabilis and Salmonella typhi isolated from bone marrow transplant patients.

The rate of infectious diseases started to be one of the major mortality agents in the healthcare sector. Exposed to increased bacterial infection by antibiotic-resistant bacteria became one of the complications that occurred for bone marrow transplant patients. Nanotechnology may provide clinicians and patients with the key to overcoming multidrug-resistant bacteria. Therefore, this study was conducted to clarify the prevalence of MDR bacteria in bone marrow transplant recipients and the use of Ag2O/ZnO nanocomposites to treat participants of diarrhea brought on by MDR bacteria following bone marrow transplantation (BMT). Present results show that pathogenic bacteria were present in 100 of 195 stool samples from individuals who had diarrhea. Phenotypic, biochemical, and molecular analysis clarify that Proteus mirabilis and Salmonella typhi were detected in 21 and 25 samples, respectively. Successful synthesis of Ag2O/ZnO nanocomposites with a particle enables to inhibition of both pathogens. The maximum inhibitory impact was seen on Salmonella typhi. At low doses (10-5 g/l), it prevented the growth by 53.4%, while at higher concentrations (10-1 g/l), Salmonella typhi was inhibited by 95.5%. Regarding Proteus mirabilis, at (10-5 g/l) Ag2O/ZnO, it was inhabited by 78.7%, but at higher concentrations (10-1 g/l), it was inhibited the growth by 94.6%. Ag2O/ZnO nanocomposite was therefore found to be the most effective therapy for MDR-isolated bacteria and offered promise for the treatment of MDR bacterial infections that cause diarrhea.

Atypical compartment syndrome of the forearm due to mixed infection with Proteus mirabilis and Morganella morganii after a penetrating injury: A limb-saving approach.

Compartment syndrome is a well-described clinical condition and is considered an orthopedic emergency affecting individuals of all ages. A typical scenario for acute compartment syndrome involves lower limb fractures or crush injuries. However, physicians may occasionally encounter atypical presentations, defined as atypical compartment syndrome (ACS). A 38-year-old, left-handed male patient without any comorbidities developed ACS of the forearm and clinical presentation of sepsis after a small penetrating injury to his right forearm. He developed ACS secondary to infected hematoma and subsequent soft tissue infection caused by Proteus mirabilis and Morganella morganii. Both bacteria infected the patient by direct contamination after injury with a knife, resulting in multifloral contamination. The patient was successfully treated with reconstructive surgery. In conclusion, ACS secondary to this type of penetrating injury shows a subtle clinical course at the time of hospital admission and can insidiously progress from an infected hematoma, posing a serious threat to the limb or even cause mortality. Good extremity function without any disability can be achieved with an accurate diagnosis during the initial evaluation of the patient in the emergency department and prompt surgical intervention followed by appropriate reconstructive methods.

Potential Antibacterial Activity of Ethanolic Curcuma longa L. Rhizome Extract Against Antibiotic-Resistant Bacteria.

<b>Background and Objective:</b> <i> Curcuma longa</i> L. rhizomes are the source of many bioactive compounds such as antitumor, antidepressant, antibacterial, anti-aging and antidiabetic. Due to the growing problem of antibiotic-resistant bacteria, it is necessary to find new sources of antibiotics. This research aimed to investigate the antibacterial activity of ethanolic <i>Curcuma longa</i> L. rhizomes extract against <i>Proteus mirabilis, Acinetobacter baumannii</i> and Multidrug-Resistant <i>Klebsiella pneumoniae</i> (MDR-K). <b>Materials and Methods:</b> Dry <i>Curcuma longa</i> L. rhizomes were extracted with ethanol. The agar diffusion method was used as the primary screening of antibacterial activity determination. The broth dilution method was used to measure the MIC and MIC of the extract. <b>Results:</b> It presented the largest diameter of the inhibition zone at 0.9 mm against <i>Proteus mirabilis</i>, followed by 0.8 mm against MDR-K. The lowest MIC and MBC values were at 0.048 and 0.39 mg mL¹ against <i>Proteus mirabilis</i>, followed by 0.195 and 6.25 mg mL¹ against MDR-K. The ethanolic <i>Curcuma longa</i> L. rhizomes extract did not affect <i>Acinetobacter baumannii</i>. <b>Conclusion:</b> The new finding of this research was that the ethanolic extract from <i>Curcuma longa</i> L. rhizomes can eliminate <i>Proteus mirabilis</i> and MDR-K that can be applied to treating antibiotic-resistant bacterial infectious diseases in the hospital.

Morphological modification of silver nanoparticles against multi-drug resistant gram-negative bacteria and cytotoxicity effect in A549 lung cancer cells through in vitro approaches.

In the present study, the individual cultures of Proteus mirabilis (P. mirabilis) and Klebsiella pneumoniae (K. pneumoniae) were treated with morphologically modified silver nanoparticles (Ag NPs) and were found to display zones of inhibition of ~ 8 mm, 16 mm, 20 mm, and 22 mm (P. mirabilis) and 6 mm, 14 mm, 20 mm, and 24 mm (K. pneumoniae) at concentrations of 25 µg/ml, 50 µg/mL, 75 µg/mL, and 100 µg/mL, respectively. In addition, turbidity tests were performed based on O. D. values, which exhibited 92% and 90% growth inhibitions at 100 µg/mL concentration for P. mirabilis and K. pneumoniae, respectively. Furthermore, the IC50 concentration of Ag NPs was established for A549 lung cancer cells and found to be at 500 µg/mL. Evidently, the morphological variation of Ag NPs treated A549 lung cancer cells was exhibited with differential morphology studied by phase-contrast microscopy. The results demonstrated that the synthesized Ag NPs was not only efficient against gram-positive bacteria but also against gram-negative bacteria and A549 cancer cells, suggesting that the potential of these biosynthesized Ag NPs is a future drug discovery source for inhibiting bacteria and cancer cells.

Spontaneous nosocomial Proteus mirabilis meningitis in a Human Immunodeficiency Virus (HIV)-infected adult patient: a case report.

BACKGROUND: Gram-negative bacillary meningitis remains a rare occurrence, even in patients with human immunodeficiency virus. Current literature only describes anecdotal cases of spontaneous nosocomial Proteus mirabilis meningitis. This report describes the clinical manifestations and management of a patient with healthcare-associated spontaneous Gram-negative bacillary meningitis in a patient with advanced human immunodeficiency virus disease. CASE PRESENTATION: A 23-year-old Congolese female was hospitalized in a human immunodeficiency virus specialized center for ongoing weight loss, chronic abdominal pain, and vomiting 9 months after initiation of treatment for tuberculosis meningitis. Hospitalization was complicated by healthcare-associated Gram-negative bacillary meningitis on day 18. Blood and cerebrospinal fluid cultures confirmed Proteus mirabilis. Antibiotic susceptibility testing showed extended spectrum beta-lactamase resistant to common antibiotics, and sensitive to meropenem. Despite initiation of high-dose meropenem by intravenous infusion (2 g every 8 hours), the patient did not improve, and died after 4 days of meropenem treatment. Gram-negative bacillary meningitis remains rare and is associated with an unfavorable prognosis. CONCLUSIONS: This case report highlights the importance of microbiological identification of pathogens in resource-limited settings. As Gram-negative bacillary meningitis does not present with pleocytosis in patients with advanced human immunodeficiency virus, a negative lumbar puncture cannot exclude this diagnosis. Access to clinical bacteriology in resource-limited settings is essential to enable correct antibiotic treatment and avoid overuse of antibiotics to which there is already resistance. It further plays an essential role in public health by identifying antibiotic susceptibilities. Infection prevention and control measures must be reinforced in order to protect patients from such avoidable healthcare-associated infections.

Evaluation of antibacterial activity of vitamin C against human bacterial pathogens / Avaliação da atividade antibacteriana da vitamina C contra patógenos bacterianos humanos

Now a day’s multidrug resistance phenomenon has become the main cause for concern and there has been an inadequate achievement in the development of novel antibiotics to treat the bacterial infections. Therefore, there is an unmet need to search for novel adjuvant. Vitamin C is one such promising adjuvant. The present study was aimed to elucidate the antibacterial effect of vitamin C at various temperatures (4°C, 37°C and 50°C) and pH (3, 8, and 11), against Gram-positive and Gram-negative bacteria at various concentrations (5-20 mg/ml) through agar well diffusion method. Growth inhibition of all bacterial strains by vitamin C was concentration-dependent. Vitamin C significantly inhibited the growth of Gram-positive bacteria: Bacillus licheniformis (25.3 ± 0.9 mm), Staphylococcus aureus (22.0 ± 0.6 mm), Bacillus subtilis (19.3 ± 0.3 mm) and Gram-negative bacteria: Proteus mirabilis (27.67 ± 0.882 mm), Klebsiella pneumoniae (21.33±0.9 mm), Pseudomonas aeruginosa (18.0 ± 1.5 mm) and Escherichia coli (18.3 ± 0.3 mm). The stability of vitamin C was observed at various pH values and various temperatures. Vitamin C showed significant antibacterial activity at acidic pH against all bacterial strains. Vitamin C remained the stable at different temperatures. It was concluded that vitamin C is an effective and safe antibacterial agent that can be used in the future as an adjunct treatment option to combat infections in humans.

Agora, a resistência antimicrobiana de um dia em patógenos aos antibióticos tornou-se a principal causa de preocupação e houve uma realização inadequada no desenvolvimento de novos antibióticos para tratar infecções bacterianas. Portanto, há uma necessidade de pesquisar um novo adjuvante, e a vitamina C é um desses adjuvantes promissores. O objetivo do presente estudo foi elucidar o efeito antibacteriano da vitamina C em diferentes temperaturas (4 °C, 37 °C e 50 °C) e pH (3, 8 e 11), contra Gram-positivos e Gram-cepas bacterianas negativas em várias concentrações (5-20 mg / ml) através do método de difusão em ágar bem. A inibição do crescimento de todas as cepas bacterianas pela vitamina C era dependente da concentração. A vitamina C inibiu significativamente o crescimento de bactérias Gram-positivas: Bacillus licheniformis (25,3 ± 0,9 mm), Staphylococcus aureus (22,0 ± 0,6 mm), Bacillus subtilis (19,3 ± 0,3 mm) e bactérias Gram- negativas: Proteus mirabilis (27,7 ± 0,9 mm), Klebsiella pneumoniae (21,3 ± 0,9 mm), Pseudomonas aeruginosa (18,0 ± 1,5 mm) e Escherichia coli (18,3 ± 0,3 mm). A estabilidade da vitamina C foi observada em vários valores de pH e várias temperaturas. A vitamina C mostrou atividade antibacteriana significativa em pH ácido contra todas as cepas bacterianas. A estabilidade da vitamina C permaneceu nas mesmas diferentes temperaturas (4 °C, 37 °C e 50 °C). Concluímos que a vitamina C é um agente antibacteriano eficaz e seguro que pode ser usado no futuro como uma opção de tratamento auxiliar para combater infecções em humanos, pois pode apoiar o sistema imunológico diretamente.

Isolation and Characterization of Lytic Proteus Virus 309.

Proteus mirabilis is frequently associated with complicated urinary tract infections (UTIs) and is the main cause of catheter-associated urinary tract infections (CAUTIs). Treatment of such infections is complicated and challenging due to the biofilm forming abilities of P. mirabilis. If neglected or mistreated, infections may lead to life-threating conditions such as cystitis, pyelonephritis, kidney failure, and bacteremia that may progress to urosepsis. Treatment with antibiotics, especially in cases of recurring and persistent infections, leads to the development of resistant strains. Recent insights into phage therapy and using phages to coat catheters have been evaluated with many studies showing promising results. Here, we describe a highly lytic bacteriophage, Proteus_virus_309 (41,740 bp), isolated from a wastewater treatment facility in Cape Town, South Africa. According to guidelines of the International Committee on Taxonomy of Viruses (ICTV), bacteriophage 309 is a species within the genus Novosibovirus. Similar to most members of the genus, bacteriophage 309 is strain-specific and lyse P. mirabilis in less than 20 min.

Expression, purification and characterization of the suppressor of copper sensitivity (Scs) B membrane protein from Proteus mirabilis.

Suppressor of copper sensitivity (Scs) proteins play a role in the bacterial response to copper stress in many Gram-negative bacteria, including in the human pathogen Proteus mirabilis. Recently, the ScsC protein from P. mirabilis (PmScsC) was characterized as a trimeric protein with isomerase activity that contributes to the ability of the bacterium to swarm in the presence of copper. The CXXC motif catalytic cysteines of PmScsC are maintained in their active reduced state by the action of its membrane-bound partner protein, the Proteus mirabilis ScsB (PmScsB). Thus, PmScsC and PmScsB form a redox relay in vivo. The predicted domain arrangement of PmScsB comprises a central transmembrane ß-domain and two soluble, periplasmic domains, the N-terminal α-domain and C-terminal γ-domain. Here, we provide a procedure for the recombinant expression and purification of the full-length PmScsB protein. Using Lemo21 (DE3) cells we expressed PmScsB and, after extraction and purification, we were able to achieve a yield of 3 mg of purified protein per 8 L of bacterial culture. Furthermore, using two orthogonal methods - AMS labelling of free thiols and a scrambled RNase A activity assay - PmScsB is shown to catalyze the reduction of PmScsC. Our results demonstrate that the PmScsC and PmScsB redox relay can be reconstituted in vitro using recombinant full-length PmScsB membrane protein. This finding provides a promising starting point for the in vitro biochemical and structural characterization of the P. mirabilis ScsC and ScsB interaction.

Analysis of pathogens and antimicrobial treatment in different groups of patients with chronic otitis media.

OBJECTIVE: Microbial infection plays an important role in exacerbation of chronic otitis media. The aim of this study was to analyse the microbiota in chronic otitis media in the context of local treatment. METHOD: In this prospective study, samples for microbiological examination were taken from 119 patients who underwent operation because of chronic otitis media. RESULTS: The results were compared between groups depending on the type of operation (none, tympanoplasty or radical), the presence of cholesteatoma or granulomatous tissue or discharge from the ear as a symptom of exacerbation. Antibiotic susceptibility of germs was analysed to define the strategy of treatment. A total of 209 samples were collected from 119 patients with chronic otitis media. CONCLUSION: Pseudomonas aeruginosa and Staphylococcus aureus were pathogens most frequently identified from the ear in the course of chronic otitis media. Pseudomonas aeruginosa was concerned with major pathology of the middle ear (radical surgery, cholesteatoma or granulomatous tissue, persisting discharge after treatment), whereas Staphylococcus aureus was obtained in dry perforations without other pathology in the middle-ear cavity. Ciprofloxacin was effective against Staphylococcus aureus, but Pseudomonas aeruginosa strains were ciprofloxacin resistant.

A Unique Case of Community Acquired Proteus mirabilis Meningitis.

Proteus mirabilis, a gram-negative bacterium commonly known for causing urinary tract infections (UTI) can rarely present with central nervous system (CNS) infections. Proteus mirabilis CNS infections are usually encountered in the neonatal and infantile period and occasionally cause brain abscesses. It is an uncommon cause of adult CNS infection. We report the first case of a community-acquired Proteus mirabilis meningitis (PMM) in a patient with Proteus mirabilis UTI, urolithiasis, and bacteremia. Risk factors for gram-negative bacillary meningitis (GNBM) include extremes of age, cancer history, diabetes mellitus, UTI, and nosocomial exposure, with the latter being a more prominent cause of PMM. Compromise of the anatomical defense against CNS infections whether accidental or neurosurgical is another important cause, and approximately two-thirds of reported cases of PMM have occurred after neurosurgical procedures. PMM patients develop fever, altered consciousness, and have an acute clinical course. Antimicrobials that can be used for treatment include third-generation cephalosporins, ciprofloxacin, imipenem/ cilastatin, aztreonam, and intraventricular aminoglycosides. Despite appropriate antibiotic therapy outcomes are poor with severe neurological deficit and death commonly resulting. Nosocomial infections can be drug-resistant and multiple antibiotics should be started while awaiting culture results. Literature review reveals that treatment with intraventricular aminoglycosides when attempted has shown bacteriological cure indicating this can be an important treatment approach. Due to the acute clinical course and high morbidity and mortality, we recommend starting multiple antibiotics with different mechanisms of action as soon as the disease is suspected. Our patient was initially started on ceftriaxone, vancomycin, acyclovir, and ampicillin for UTI and meningoencephalitis. The antibiotics were later consolidated to cefepime based on blood, urine and, cerebrospinal fluid cultures growing pan-sensitive Proteus mirabilis. Her clinical condition continued to worsen and ciprofloxacin was added. However, due to the progressive decline in her condition, the family elected for inpatient hospice care and intraventricular aminoglycosides were not attempted.

Structural elucidation, mechanism of action, antibacterial proficiency and synergistic forte of purified Euphorbia hirta whole plant extract against multi-drug resistant otitis media infection / Elucidación estructural, mecanismo de acción, competencia antibacteriana y fuerza sinérgica del extracto de planta entera de Euphorbia hirta purificado contra la infección por otitis media resistente a múltiples fármacos

This study investigated the antibacterial potential of Euphorbia hirtawhole plant extracts, honey and conventional antibiotics and their synergistic effects against selected multidrug resistant and typed bacterial strains associated with otitis media. E. hirtawhole plant extract was purified using column chromatography technique. The antibacterial assays of extracts were done using standard microbiological procedures. Protein, sodium and potassium ion leakage of the synergistic mixtures was determined using flame-photometry. At 100 mg/ml, acetone extracts presented highest inhibition against S. aureus (NCTC 6571) with 32 ± 0.83 mm zone of inhibition. The fractional inhibitory concentration indices displayed higher synergism in combination of plant extract, honey and ciprofloxacin against P. mirabilisat 0.02 compared to drug combination synergy standard (≤ 0.5). This work revealed augmentation of ciprofloxacin potency when combined with purified E. hirta acetone extract and honey and implies their high potential in the treatment of multidrug resistant infectionof otitis media.

Este estudio investigó el potencial antibacteriano de extractos de plantas enteras de Euphorbia hirta, miel y antibióticos convencionales y sus efectos sinérgicos contra cepas bacterianas seleccionadas multirresistentes y tipificadas asociadas con la otitis media. El extracto de la planta entera de E. hirtase purificó usando la técnica de cromatografía en columna. Los ensayos antibacterianos de extractos se realizaron utilizando procedimientos microbiológicos estándar. La fuga de iones de proteínas, sodio y potasio de las mezclas sinérgicas se determinó mediante fotometría de llama. A 100 mg/ml, los extractos de acetona presentaron la mayor inhibición contra S. aureus (NCTC 6571) con una zona de inhibición de 32 ± 0,83 mm. Los índices de concentración inhibitoria fraccional mostraron un mayor sinergismo en combinación de extracto de planta, miel y ciprofloxacina contra P. mirabilisa 0,02 en comparación con el estándar de sinergia de combinación de fármacos (≤ 0,5). Este trabajo reveló un aumento de la potencia de la ciprofloxacina cuando se combina con extracto de acetona purificado de E. hirtay miel e implica sualto potencial en el tratamiento de infecciones de otitis media resistentes a múltiples fármacos.

Caracterización de la infección urinaria y resistencia antimicrobiana en receptores de trasplante renal de un centro colombiano / Characterization of Urinary Tract Infection and Antimicrobial Resistance in Kidney Transplant Recipients from a Colombian Tertiary Center

La infección del tracto urinario (ITU) es una de las principales complicaciones postrasplante renal, los datos a nivel nacional en ese grupo poblacional son limitados. Objetivos caracterizar la microbiología de las ITU presentadas en receptores de trasplante renal (TxR) en un centro colombiano durante el periodo 2017­2019, los factores relacionados con la resistencia antimicrobiana y el impacto de la ITU en la función del injerto renal. Métodos estudio de corte transversal ejecutado mediante el análisis de la base de datos de ingresos hospitalarios por urgencias de pacientes receptores de TxR con sospecha clínica de ITU en una institución de cuarto nivel en Bogotá, Colombia. El análisis de datos se ejecutó en STATA 13.0. Resultados La ITU causó 12,69% de visitas a urgencias en pacientes trasplantados. Los microorganismos aislados fueron: Escherichia coli 52,22%, Klebsiella pneumoniae 16,67%, Pseudomonas aeruginosa 4,44%, Salmonella spp 4,44%, Proteus mirabilis 3,33%, Serratia marcescens 2,22%, Klebsiella oxytoca 2,22%, Citrobacter koseri 1,11%, Enterobacter cloacae 1,11%, otros 2,22%; El urocultivo fue negativo en 10% de los casos. El 28,39% (n:23) de gérmenes aislados fue multisensible mientras que el 71,60% (n:58) expresó algún tipo de patrón de resistencia distribuido así: 68,96% productor de betalactamasa de espectro extendido (BLEE), 15,52% productor de carbapenemasas, 12,06% productor de betalactamasa tipo IRT, 3,45% fue catalogado como multirresistente. 17,78% de los pacientes presentó criterios de urosepsis, no se registró ningún caso de mortalidad asociada a la ITU. La creatinina sérica tuvo un incremento promedio de 0,46 mg/dl durante el episodio de ITU (p: <0,0001) y el antecedente de diabetes mellitus se relacionó con la ITU causada por gérmenes resistentes (p: 0,008). Conclusiones La ITU es una causa frecuente de atención en urgencias para pacientes receptores de TxR; la Escherichia coli es el microorganismo causal más frecuente y cerca del 70% de los gérmenes aislados presentó algún patrón de resistencia antimicrobiana.

Urinary tract infection (UTI) is one of the most common complications after kidney transplantation (KTx). This study aims to characterize the microbiology of UTIs presented in KTx recipients in a Colombian tertiary center during the period 2017­2019, factors related with antimicrobial resistance and the impact of UTI on kidney graft function. Methods A cross-sectional retrospective single center study were made through the institutional database analysis of hospital admissions to the emergency room of KTx recipients with clinical suspicion of UTI. Data analysis was run on STATA 13.0. Results UTI caused 12.69% of visits to the emergency room in transplant patients during the study period. The isolated microorganisms were Escherichia coli 52.22%, Klebsiella pneumoniae 16.67%, Pseudomonas aeruginosa 4.44%, Salmonella spp 4.44%, Proteus mirabilis 3.33%, Serratia marcescens 2.22%, Klebsiella oxytoca 2.22%, Citrobacter koseroi 1.11%, others 2.22%; Urine culture was negative in 10% of cases. 28.39% (n: 23) of isolated germs were multisensitive while 71.60% (n: 58) expressed some type of resistance pattern distributed as follows: 68.96% extended spectrum beta-lactamase (ESBL) producers, 15.52% carbapenemases producers, 12.06% IRT-type beta-lactamase producers, 3.45% was classified as multi-resistant. 17.78% of patients presented criteria for urosepsis, there was no cases of mortality due to UTI. Serum creatinine had an average increase of 0.46 mg/dl during the UTI episode (p: <0.0001) and a history of diabetes mellitus was related with UTI caused by resistant germs (p: 0.008). Conclusion UTI is a frequent cause of emergency care for KTx recipients. E. coli is the most common causative microorganism and about 70% of isolated germs showed some pattern of antimicrobial resistance.

In vitro activity of hyperthermia on swarming motility and antimicrobial susceptibility profiles of Proteus mirabilis isolates.

AIM: Swarming motility is a virulence factor for Proteus mirabilis and is a coordinated multicellular movement of bacteria. In this study, we investigated the inhibitory effect of hyperthermia on bacterial swarming motility and antimicrobial resistance. METHODS: Thirty-one P. mirabilis isolates were included in the study. Seven inoculated agar plates were incubated inside incubators with increasing temperature levels: at 36 °C (control) and 40-45 °C. On the next day, inhibition of swarming was evaluated and minimum paralyzing temperature (MPT) values were determined. An antimicrobial susceptibility test (antibiogram) is performed by exposing bacteria to increasing concentrations of antibiotics, in vitro. Thus, we used the Kirby-Bauer disk diffusion test as a screening method to analyze the antibiogram profiles of the isolates at 36 °C and 42 °C. Finally, a time-kill assay was performed to analyze the killing effect of hyperthermia (42 °C) on planktonic bacteria, in combination with the antibiotic meropenem at the first and third hours. A Wilcoxon signed-rank test was used to compare the killing effects of meropenem, hyperthermia and their combinations. RESULTS: The median MPT value was determined as 44 °C. In the disk diffusion assay, susceptibility development was observed in 94% of isolates for at least one antibiotic. In the time-kill assay, we observed a significant killing effect of hyperthermia in combination with meropenem. Under the microscope, we observed the formation of spherical cells by the effect of heat. CONCLUSION: We conclude that these findings might be useful when employing the hyperthermia method to treat infectious diseases caused by P. mirabilis in the future.

Proteus mirabilis thoracic vertebral osteomyelitis: a case report.

BACKGROUND: Proteus mirabilis is the second most common pathogen that causes urinary tract infections after Escherichia coli. In rare cases, it is associated with vertebral osteomyelitis. The underlying mechanism of this relationship may be related to the retrograde dissemination of bacteria through the paravertebral venous plexus. CASE PRESENTATION: We report a case of an 80-year-old Taiwanese woman who had recurrent episodes of fever and chronic back pain for 1 year. All blood cultures were positive for P. mirabilis. Inflammation scans and magnetic resonance imaging revealed a previously undetected vertebral lesion between the seventh and eighth thoracic vertebra. She responded well to treatment with antibiotics, reporting considerable relief of back pain and no fever recurrence at the 4-month follow-up. CONCLUSIONS: Chronic back pain is a common but often dismissed symptom among the older population; osteomyelitis should be considered in patients with recurrent fever or neurological symptoms. Old age, chronic renal failure, and diabetes mellitus are possible predisposing factors for osteomyelitis. Our findings suggest that long-term treatment with antibiotics is effective for osteomyelitis caused by P. mirabilis,, although surgery is required for abscess formation or serious vertebral destruction.

Synthesis, Characterization, Molecular Docking, In Vitro Biological Evaluation and In Vitro Cytotoxicity Study of Novel Thiazolidine-4-One Derivatives as Anti-Breast Cancer Agents.

BACKGROUND: Thiazolidine-4-one is a promising class of heterocyclic compounds with interesting pharmacological and biological activities, such as anticancer and antibacterial. Therefore, many researchers have synthesized thiazolidine-4-ones and evaluated their biological potential for developing new drugs. OBJECTIVE: In this study, two novel thiazolidine-4-one derivatives (T1 and T2) were synthesized and evaluated for their antibacterial activity toward Staphylococcus aureus, Escherichia coli, and Proteus mirabilis. Also, the cytotoxic activities of compounds T1 and T2 were estimated against MCF-7 (HER2+, ER+, and ER+) and MDAMB- 231 (triple-negative) human breast cancer cell lines. The chemical structures of the compounds T1 and T2 were proven using spectral techniques (FT-IR, 1HNMR, and 13CNMR) and CHN elemental analysis. METHODS: The synthesis of thiazolidine-4-one compounds was performed in two steps. The first step consisted of the formation of Schiff bases S1 and S2. In the second step, the synthesized Schiff bases were reacted with thioglycolic acid to prepare thiazolidine-4-one compounds. Hemolysis assay, molecular docking, cytotoxicity activity (MTT assay), and antibacterial activity (disc diffusion assay) were studied. RESULTS: The hemolysis study demonstrated that the hemolytic ratio of compounds T1 and T2 at (1, 2, and 3) mg/ml was less than 4%. MTT assay showed that 100 µg/ml of compounds T1 and T2 diminish the MCF-7 cell growth up to 80.05 ± 1.72 and 69.85 ± 3.26 respectively after 72hr., while the same concentration of compounds T1 and T2 reduces the MDA-MB-231 cell growth up 70.28 ± 2.31 and 57.15 ± 1.49, respectively. The inhibition zones of T1 and T2 were 12 mm at 50 mg/ml and 10 mm at 5 mg/ml in E. coli bacteria. Furthermore, a docking study was carried out to investigate the affinity and binding mode of compounds T1 and T2 towards the ERα, VEGF, and HER2 protein receptors in breast cancer cells. Data obtained from the docking study were exactly identical to that obtained from in vitro cytotoxicity assay. CONCLUSION: The results proved that T1 is an optimal anticancer agent toward breast cancer cells and the hemolysis study indicates the use of safety inside the body for compound T1. Synthesized compound T1 was most effective against MCF-7 cells compared to MDA-MB-231 cells and more effective than the reference drug tamoxifen in breast cell lines. The high cytotoxicity of T1 on the growth of MCF-7 cells because T1 binds with a high degree of affinity to the estrogen and HER2 receptors, which in turn inhibits cell proliferation and induces apoptosis.

The 'Shape-Shifter' Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences.

Multiple crystal structures of the homo-trimeric protein disulphide isomerase PmScsC reveal that the peptide which links the trimerization stalk and catalytic domain can adopt helical, ß-strand and loop conformations. This region has been called a 'shape-shifter' peptide. Characterisation of this peptide using NMR experiments and MD simulations has shown that it is essentially disordered in solution. Analysis of the PmScsC crystal structures identifies the role of intermolecular contacts, within an assembly of protein molecules, in stabilising the different linker peptide conformations. These context-dependent conformational properties may be important functionally, allowing for the binding and disulphide shuffling of a variety of protein substrates to PmScsC. They also have a relevance for our understanding of protein aggregation and misfolding showing how intermolecular quaternary interactions can lead to ß-sheet formation by a sequence that in other contexts adopts a helical structure. This 'shape-shifting' peptide region within PmScsC is reminiscent of one-to-many molecular recognition features (MoRFs) found in intrinsically disordered proteins which are able to adopt different conformations when they fold upon binding to their protein partners.