Perceived stressors of climate vulnerability across scales in the Savannah zone of Ghana: a participatory approach

Smallholder farmers in sub-Saharan Africa are confronted with climatic and non-climatic stressors. Research attention has focused on climatic stressors, such as rainfall variability, with few empirical studies exploring non-climatic stressors and how these interact with climatic stressors at multiple scales to affect food security and livelihoods. This focus on climatic factors restricts understanding of the combinations of stressors that exacerbate the vulnerability of farming households and hampers the development of holistic climate change adaptation policies. This study addresses this particular research gap by adopting a multi-scale approach to understand how climatic and non-climatic stressors vary, and interact, across three spatial scales (household, community and district levels) to influence livelihood vulnerability of smallholder farming households in the Savannah zone of northern Ghana. This study across three case study villages utilises a series of participatory tools including semi-structured interviews, key informant interviews and focus group discussions. The incidence, importance, severity and overall risk indices for stressors are calculated at the household, community, and district levels. Results show that climatic and non-climatic stressors were perceived differently; yet, there were a number of common stressors including lack of money, high cost of farm inputs, erratic rainfall, cattle destruction of crops, limited access to markets and lack of agricultural equipment that crossed all scales. Results indicate that the gender of respondents influenced the perception and severity assessment of stressors on rural livelihoods at the community level. Findings suggest a mismatch between local and district level priorities that have implications for policy and development of agricultural and related livelihoods in rural communities. Ghana’s climate change adaptation policies need to take a more holistic approach that integrates both climatic and non-climatic factors to ensure policy coherence between national climate adaptation plans and District development plans

CATIONIC AMPHIPHILIC INDOLES: SYNTHESIS AND EVALUATION AS ANTIMYCOBACTERIAL AGENTS

Ph.DDOCTOR OF PHILOSOPH

Resistance against membrane-inserting MmpL3 inhibitor through upregulation of MmpL5 in M. tuberculosis.

10.1128/AAC.01100-20Antimicrob Agents Chemothe

Amphiphilic Indole Derivatives as Antimycobacterial Agents: Structure-Activity Relationships and Membrane Targeting Properties

10.1021/acs.jmedchem.6b01530JOURNAL OF MEDICINAL CHEMISTRY6072745-276

Amide-Amine Replacement in Indole-2-carboxamides Yields Potent Mycobactericidal Agents with Improved Water Solubility

10.1021/acsmedchemlett.0c00588ACS MEDICINAL CHEMISTRY LETTERS125704-71

Amphiphilic Indole Derivatives as Antimycobacterial Agents: Structure–Activity Relationships and Membrane Targeting Properties

Antibacterials that disrupt cell membrane function have the potential to eradicate “persister” organisms and delay the emergence of resistance. Here we report the antimycobacterial activities of 4-fluoro and 6-methoxyindoles bearing a cationic amphiphilic motif represented by a lipophilic <i>n</i>-octyl side chain at position 1 and a positively charged azepanyl or 1,4-dioxa-8-azaspiro[4.5]­decane moiety at position 3. These analogues exhibited balanced profiles of potency (<i>Mycobacterium bovis</i> BCG, <i>M tuberculosis</i> H37Rv), selective activity, solubility, and metabolic stability. Bacteriological mechanism of action investigations on a representative analogue revealed cell membrane permeabilization and depolarization in <i>M bovis</i> BCG. These membrane-related changes preceded cell death indicating that the loss in membrane integrity was not an epiphenomenon. Bactericidal activity was observed against both growing and nongrowing mycobacterial cultures. The analogue also upregulated cell envelope stress-inducible promoters p<i>ini</i>BAC and p<i>clg</i>R, implicating the involvement of envelope-related targets in its mode of action

Indolyl Azaspiroketal Mannich Bases Are Potent Antimycobacterial Agents with Selective Membrane Permeabilizing Effects and in Vivo Activity

The inclusion of an azaspiroketal Mannich base in the membrane targeting antitubercular 6-methoxy-1-<i>n</i>-octyl-1<i>H</i>-indole scaffold resulted in analogs with improved selectivity and submicromolar activity against <i>Mycobacterium tuberculosis</i> H37Rv. The potency enhancing properties of the spiro-fused ring motif was affirmed by SAR and validated in a mouse model of tuberculosis. As expected for membrane inserting agents, the indolyl azaspiroketal Mannich bases perturbed phospholipid vesicles, permeabilized bacterial cells, and induced the mycobacterial cell envelope stress reporter promoter p<i>iniBAC</i>. Surprisingly, their membrane disruptive effects did not appear to be associated with bacterial membrane depolarization. This profile was not uniquely associated with azaspiroketal Mannich bases but was characteristic of indolyl Mannich bases as a class. Whereas resistant mycobacteria could not be isolated for a less potent indolyl Mannich base, the more potent azaspiroketal analog displayed low spontaneous resistance mutation frequency of 10^–8/CFU. This may indicate involvement of an additional envelope-related target in its mechanism of action

Potency Increase of Spiroketal Analogs of Membrane Inserting Indolyl Mannich Base Antimycobacterials Is Due to Acquisition of MmpL3 Inhibition.

10.1021/acsinfecdis.0c00121ACS Infect Di