Siderophores: A Novel Approach to Fight Antimicrobial Resistance

ABSTRACT Antibiotics that are excreted into the intestinal tract promote antibiotic resistance by exerting selective pressure on the gut microbiota. Using a beagle dog model, we show that an orally administered targeted recombinant β-lactamase enzyme eliminates the portion of parenteral ampicillin that is excreted into the small intestine, preventing ampicillin-induced changes to the fecal microbiota without affecting ampicillin levels in serum. In dogs receiving ampicillin, significant disruption of the fecal microbiota and the emergence of ampicillin-resistant Escherichia coli and TEM genes were observed, whereas in dogs treated with ampicillin in combination with an oral β-lactamase, these did not occur. These results suggest a new strategy for reducing antimicrobial resistance in humans.

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Genetic Contexts ofblaNDM-1in Patients Carrying Multiple NDM-Producing Strains

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01319-15 ◽

2015 ◽

Vol 59 (12) ◽

pp. 7405-7410 ◽

Cited By ~ 25

Author(s):

Alexander M. Wailan ◽

Anna L. Sartor ◽

Hosam M. Zowawi ◽

John D. Perry ◽

David L. Paterson ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Bacterial Species ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

Gram Negative ◽

Content Type ◽

Novel Approach ◽

Plasmid Replicon ◽

Underlying Mechanisms ◽

Genetic Context

ABSTRACTThe carbapenem resistance determinantblaNDM-1has been found in various Gram-negative bacteria and upon different plasmid replicon types (Inc). Here, we present four patients within two hospitals in Pakistan harboring between two and four NDM-1-producing Gram-negative bacilli of different species coresident in their stool samples. We characterize theblaNDM-1genetic contexts of these 11 NDM-1-producing Gram-negative bacilli in addition to other antimicrobial resistance mechanisms, plasmid replicon profiles, and sequence types (STs) in order to understand the underlying acquisition mechanisms of carbapenem resistance within these bacteria. Two common plasmid types (IncN2 and IncA/C) were identified to carryblaNDM-1among the six different bacterial species isolated from the four patients. Two of these strains were novelCitrobacter freundiiST 20 and ST 21. The same IncN2-typeblaNDM-1genetic context was found in all four patients and within four different species. The IncA/C-typeblaNDM-1genetic context was found in two different species and in two of the four patients. Combining genetic context characterization with other molecular epidemiology methods, we were able to establish the molecular epidemiological links between genetically unrelated bacterial species by linking their acquisition of an IncN2 or IncA/C plasmid carryingblaNDM-1for carbapenem resistance. By combining plasmid characterization and in-depth genetic context assessment, this analysis highlights the importance of plasmids in antimicrobial resistance. It also provides a novel approach for investigating the underlying mechanisms ofblaNDM-1-related spread between bacterial species and genera via plasmids.

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Essential Oils: A Novel Approach for Anti-Microbial Therapy

The Natural Products Journal ◽

10.2174/2210315511666210906114009 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ashwini Wani ◽

Hiren Mange ◽

Aishwarya Vasudevan

Keyword(s):

Antimicrobial Resistance ◽

Essential Oils ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Antimicrobial Properties ◽

Rational Approach ◽

Ability To Act ◽

Novel Approach ◽

New Antibiotics ◽

Potential Applications

: Overexploitation of antibiotics has led to significant challenges with antimicrobial resistance. The gravity of this trend has resulted in the rapid emergence of multi-resistant pathogens. Increased frequency to treat infections and the unfeasibility to reverse this resistance have burdened researchers in developing novel mechanisms to counteract and obstruct antimicrobial resistance. An effective medical strategy to control resistance was to develop new and potent antibiotics although, a sobering reality is that the product pipeline towards new antibiotics is inadequate. To ensure continued effective treatment of bacterial infections, there is an urgent need to control as well as conserve existing antibiotics through novel approaches. Utilization of Essential Oils (EO) in a multi-target anti-infective therapy addresses this need by targeting the mechanism of bacterial resistance and discovering synergism between EO’s antimicrobial properties to anti-infectives. When introduced into a pharmaceutical formulation, this novel and rational approach will open the door towards the development of a new generation of antimicrobials. Today, several essential oils have the ability to act as resistant modifying agents and enhance the antimicrobial activity of anti-infectives. This review article intends to focus on the effectiveness of essential oils on drug-resistant pathogens, mechanisms to counteract antimicrobial resistance, approaches to enhance efficacy, and explore potential applications.

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Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

Biochemical Journal ◽

10.1042/bcj20190591 ◽

2019 ◽

Vol 476 (24) ◽

pp. 3705-3719 ◽

Cited By ~ 2

Author(s):

Avani Vyas ◽

Umamaheswar Duvvuri ◽

Kirill Kiselyov

Keyword(s):

Oxidative Stress ◽

Head And Neck ◽

Transcriptional Activation ◽

Platinum Resistance ◽

Mrna Levels ◽

Strong Positive Correlation ◽

Platinum Compounds ◽

Copper Chelation ◽

Novel Approach ◽

Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

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Collecting Words: A Clinical Example of a Morphology-Focused Orthographic Intervention

Language Speech and Hearing Services in Schools ◽

10.1044/2020_lshss-19-00050 ◽

2020 ◽

Vol 51 (3) ◽

pp. 544-560 ◽

Cited By ~ 3

Author(s):

Kimberly A. Murphy ◽

Emily A. Diehm

Keyword(s):

Written Language ◽

Morphological Knowledge ◽

English Orthography ◽

Word Level ◽

Novel Approach ◽

Language Pathology ◽

The One ◽

Critical Intervention ◽

Reading And Spelling ◽

Reading And Spelling Difficulties

Purpose Morphological interventions promote gains in morphological knowledge and in other oral and written language skills (e.g., phonological awareness, vocabulary, reading, and spelling), yet we have a limited understanding of critical intervention features. In this clinical focus article, we describe a relatively novel approach to teaching morphology that considers its role as the key organizing principle of English orthography. We also present a clinical example of such an intervention delivered during a summer camp at a university speech and hearing clinic. Method Graduate speech-language pathology students provided a 6-week morphology-focused orthographic intervention to children in first through fourth grade ( n = 10) who demonstrated word-level reading and spelling difficulties. The intervention focused children's attention on morphological families, teaching how morphology is interrelated with phonology and etymology in English orthography. Results Comparing pre- and posttest scores, children demonstrated improvement in reading and/or spelling abilities, with the largest gains observed in spelling affixes within polymorphemic words. Children and their caregivers reacted positively to the intervention. Therefore, data from the camp offer preliminary support for teaching morphology within the context of written words, and the intervention appears to be a feasible approach for simultaneously increasing morphological knowledge, reading, and spelling. Conclusion Children with word-level reading and spelling difficulties may benefit from a morphology-focused orthographic intervention, such as the one described here. Research on the approach is warranted, and clinicians are encouraged to explore its possible effectiveness in their practice. Supplemental Material https://doi.org/10.23641/asha.12290687

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