OBJECTIVE -To determine the microbiological profile and antibiotic susceptibility patterns of organisms isolated from diabetic foot ulcers. Also, to assess potential risk factors for infection of ulcers with multidrug-resistant organisms (MDROs) and the outcome of these infections.RESEARCH DESIGN AND METHODS -Pus samples for bacterial culture were collected from 80 patients admitted with diabetic foot infections. All patients had ulcers with Wagner's grade 3-5. Fifty patients (62.5%) had coexisting osteomyelitis. Gram-negative bacilli were tested for extended spectrum -lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method, disc diffusion, and mec A-based PCR. Potential risk factors for MDRO-positive samples were explored.RESULTS -Gram-negative aerobes were most frequently isolated (51.4%), followed by gram-positive aerobes and anaerobes (33.3 and 15.3%, respectively). Seventy-two percent of patients were positive for MDROs. ESBL production and methicillin resistance was noted in 44.7 and 56.0% of bacterial isolates, respectively. MDRO-positive status was associated with presence of neuropathy (P ϭ 0.03), osteomyelitis (P ϭ 0.01), and ulcer size Ͼ4 cm 2 (P Ͻ 0.001) but not with patient characteristics, ulcer type and duration, or duration of hospital stay. MDRO-infected patients had poor glycemic control (P ϭ 0.01) and had to be surgically treated more often (P Ͻ 0.01). CONCLUSIONS -Infection withMDROs is common in diabetic foot ulcers and is associated with inadequate glycemic control and increased requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications. Diabetes Care 29:1727-1732, 2006W orldwide, diabetic foot lesions are a major medical, social, and economic problem and are the leading cause of hospitalization for patients with diabetes. Infectious agents are associated with amputation of the infected foot if not treated promptly.Proper management of these infections requires appropriate antibiotic selection based on culture and antimicrobial susceptibility results; however, initial management comprises empirical antimicrobial therapy, which is often based on susceptibility data extrapolated from studies performed on general clinical isolates (1). Several studies found methicillin-resistant Staphylococcus aureus (MRSA) in as many as 15-30% of diabetic wounds (1-3). Infection with multidrug-resistant organisms (MDROs) may increase the duration of hospital stay and cost of management and may cause additional morbidity and mortality (4). Although increasing antimicrobial resistance is a pertinent problem in India, there is paucity of data on the frequency of MDRO infections and the outcome of such infections among diabetic foot ulcers in this region. The aim of this study was to determine the microbiological and antimicrobial susceptibility profile of organisms isolated from patients with diab...
Monothiol glutaredoxins play a crucial role in iron-sulfur (Fe/S) protein biogenesis. Essentially all of them can coordinate a [2Fe-2S] cluster and have been proposed to mediate the transfer of clusters from scaffold proteins to target apo proteins, possibly by acting as cluster transfer proteins. The molecular basis of cluster transfer from monothiol glutaredoxins to target proteins is a fundamental, but still unresolved, aspect to be defined in Fe/S protein biogenesis. In mitochondria monothiol glutaredoxin 5 (GRX5) is involved in the maturation of all cellular Fe/S proteins and participates in cellular iron regulation. Here we show that the structural plasticity of the dimeric state of the [2Fe-2S] bound form of human GRX5 (holo hGRX5) is the crucial factor that allows an efficient cluster transfer to the partner proteins human ISCA1 and ISCA2 by a specific protein-protein recognition mechanism. Holo hGRX5 works as a metallochaperone preventing the [2Fe-2S] cluster to be released in solution in the presence of physiological concentrations of glutathione and forming a transient, cluster-mediated protein-protein intermediate with two physiological protein partners receiving the [2Fe-2S] cluster. The cluster transfer mechanism defined here may extend to other mitochondrial [2Fe-2S] target proteins.Fe/S protein maturation | [2Fe-2S] cluster transfer mechanism | monothiol Grxs | NMR G lutaredoxins (Grxs) and glutathione (GSH) are universally distributed among all organisms, and they have been shown to play a fundamental role in iron-sulfur (Fe/S) protein biogenesis (1-5). Specifically, the [2Fe-2S]-bound forms of monothiol Grxs and a [2Fe-2S]-glutathione complex are the species suggested to be responsible for trafficking [2Fe-2S] clusters within the cell (6-9). The current working model is that in the cell monothiol Grxs receive a [2Fe-2S] cluster from the scaffold protein ISCU (where de novo synthesis of the [2Fe-2S] cluster occurs) and transfer it to specific targeting proteins, which then facilitate Fe/S cluster insertion into the final acceptor apo protein (7, 10, 11). Another possible cluster transfer mechanism, which has been proposed (8), hypothesizes the cellular presence of a [2Fe-2S](GS) 4 complex, which could transiently store [2Fe-2S] clusters, facilitate cluster exchange with the cellular Fe/S cluster biosynthesis machineries, and regulate the biosynthesis of Fe/S clusters. However, a drawback of the latter model is that all of the Fe/S cellular trafficking processes will result to be protein-independent and therefore highly unspecific, thus potentially inflicting severe cellular damage.The mitochondrial, monothiol glutaredoxin 5 protein (GRX5) belongs to the core part of the mitochondrial Fe/S cluster (ISC) assembly system (10, 12, 13), is required in the maturation of all cellular [2Fe-2S] and [4Fe-4S] proteins (11), and participates in cellular iron regulation (14). Human GRX5 in vitro binds a [2Fe-2S] cluster (15) and yeast GRX5, which in vivo and in vitro binds a [2Fe-2S] cluster (11), has been...
Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly evolved into a pandemic. Though its origin has been linked to the Wuhan City of China's Hubei Province in December 2019, recent reports claim that the original animalto-human transmission of the virus probably happened sometime between September and October 2019 in Guangdong Province, rather than Hubei. As of July 3, 2020, India has reported a case positivity rate of 6.5% and a fatality rate of 2.8%, which are among the lowest in the world. Also, the severity of the disease is much less among Indians as evidenced by the low rate of ICU admission (15.3%) and the need for mechanical ventilation (4.16%). As per the World Health Organization (WHO) situation report 165 on July 3, 2020, India has one of the lowest deaths per 100,000 population (1.32 deaths against a global average of 6.04). Several factors related to the pathogen, host and environment might have some role in reducing the susceptibility of Indians to COVID-19. These include some ongoing mutations that can alter the virulence of the circulating SARS-CoV-2 strains, host factors like innate immunity, genetic diversity in immune responses, epigenetic factors, genetic polymorphisms of ACE2 receptors, micro RNAs and universal BCG vaccination, and environmental factors like high temperature and humidity which may alter the viability and transmissibility of the strain. This perspective-highlights the potential factors that might be responsible for the observed low COVID-19 fatality rate in Indian population. It puts forward several hypotheses which can be a ground for future studies determining individual and population susceptibility to COVID-19 and thus, may offer a new dimension to our current understanding of the disease.
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