Microbial pathogens that cause severe infections and are resistant to drugs are simultaneously becoming more active. This urgently calls for novel effective antibiotics. Organisms from extreme environments are known to synthesize novel bioprospecting molecules for biomedical applications due to their peculiar characteristics of growth and physiological conditions. Antimicrobial developments from hypersaline environments, such as lagoons, estuaries, and salterns, accommodate several halophilic microbes. Salinity is a distinctive environmental factor that continuously promotes the metabolic adaptation and flexibility of halophilic microbes for their survival at minimum nutritional requirements. A genetic adaptation to extreme solar radiation, ionic strength, and desiccation makes them promising candidates for drug discovery. More microbiota identified via sequencing and ‘omics’ approaches signify the hypersaline environments where compounds are produced. Microbial genera such as Bacillus, Actinobacteria, Halorubrum and Aspergillus are producing a substantial number of antimicrobial compounds. Several strategies were applied for producing novel antimicrobials from halophiles including a consortia approach. Promising results indicate that halophilic microbes can be utilised as prolific sources of bioactive metabolites with pharmaceutical potentialto expand natural product research towards diverse phylogenetic microbial groups which inhabit salterns. The present study reviews interesting antimicrobial compounds retrieved from microbial sources of various saltern environments, with a discussion of their potency in providing novel drugs against clinically drug-resistant microbes.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasingly causing morbidity and mortality; thus, drugs with multifunctional efficacy against MRSA are needed. We extracted a novel compound from the halophilic Pseudomonas aeruginosa using an ethyl acetate (HPAEtOAcE). followed by purification and structure elucidation through HPLC, LCMS, and ¹H and ¹³C NMR, revealing the novel 5-(1H-indol-3-yl)-4-pentyl-1,3-oxazole-2-carboxylic acid (Compound 1). Molecular docking of the compound against the MRSA PS (pantothenate synthetase) protein was confirmed using the CDOCKER algorithm in BDS software with specific binding to the amino acids Arg (B:188) and Lys (B:150) through covalent hydrogen bonding. Molecular dynamic simulation of RMSD revealed that the compound–protein complex was stabilized. The proficient bioactivities against MRSA were attained by the HPAEtOAcE, including MIC and MBCs, which were 0.64 and 1.24 µg/mL, respectively; 100% biomass inhibition and 99.84% biofilm inhibition were observed with decayed effects by CLSM and SEM at 48 h. The hla, IrgA, and SpA MRSA genes were downregulated in RT-PCR. Non-hemolytic and antioxidant potential in the DPPH assay were observed at 10 mg/mL and IC₅₀ 29.75 ± 0.38 by the HPAEtOAcE. In vitro growth inhibition assays on MRSA were strongly supported by in silico molecular docking; Lipinski’s rule on drug-likeness and ADMET toxicity prediction indicated the nontoxic nature of compound.