Lop Nur, an extremely arid environment, harbors unique microbial resources and represents a potential reservoir for novel bioactive substances. With antibiotic resistance becoming an increasing global concern, the resistance traits of microorganisms in extreme habitats and their potential association with antibacterial activity remain poorly understood. This study aimed to investigate the diversity of soil microorganisms in Lop Nur, their resistance to norfloxacin, kanamycin, and amoxicillin, and their inhibitory activity against common pathogenic bacteria, thereby providing a scientific basis for the discovery of new antibacterial candidates. Surface soils from three sampling points in Lop Nur were inoculated onto Gao’s No.1 and LB media supplemented with different antibiotic regimens (single, pairwise, and triple combinations). Isolates were identified by 16S rRNA gene sequencing, their antibiotic resistance was assessed using the disk diffusion method, and antibacterial activity was evaluated using the agar well diffusion method. A total of 120 microorganisms were isolated, belonging to six phyla and nine genera, including 10 potential new species. The control group yielded the highest diversity (35 strains), whereas only 4 strains were recovered under triple-antibiotic treatment, demonstrating the strong selective effect of antibiotic stress. Resistance profiling showed that 88.14% of strains were resistant to amoxicillin, 64.71% to norfloxacin, and 60.68% to kanamycin, with multidrug resistance being widespread. Eleven strains exhibited antibacterial activity against five pathogens, including Staphylococcus aureus (maximum inhibition zone 53.51 mm), and nine of these strains also displayed antibiotic resistance, suggesting a potential association between resistance and antibacterial activity. Microorganisms isolated from Lop Nur displayed extensive resistance and notable antibacterial activity. Antibiotic stress strongly influenced the cultivable microbial isolates, facilitating the recovery of resistant strains with antibacterial potential. These findings provide a valuable reference for exploring microbial resources in extreme environments and highlight the potential link between antibiotic resistance and antibacterial activity.

Understanding how cultivation conditions influence the recovery of microbial diversity is critical for interpreting cultivation-derived communities in relation to in situ microbial ecology, particularly in nutrient-limited environments such as desert soils. In this study, we investigated how an oligotrophic nutrient gradient shapes cultivation outcomes and enrichment-derived bacterial community structure in soils from the Taklimakan Desert. Three enrichment treatments representing decreasing nutrient availability—standard low-nutrient medium (R2A), diluted medium (DR2A), and sterile water—were used to compare enrichment-derived communities with the original soil microbiome. Amplicon sequencing revealed that cultivation substantially altered community composition and reduced both taxonomic richness and diversity relative to the original soil. Across enrichment treatments, bacterial communities were dominated by a limited number of taxa, whereas the original soil contained a broader range of low-abundance lineages. Within the enrichment system, variation in nutrient supply influenced the relative abundance of specific taxa, with differential responses observed at the genus level. In contrast, beta diversity analysis showed only limited separation among enrichment treatments, and co-occurrence network analysis indicated generally simple and weakly connected community structures across all conditions. Overall, our results demonstrate that cultivation represents the primary selective force shaping enrichment-derived bacterial communities, while nutrient supply intensity acts as a secondary modulator of taxon-specific enrichment. These findings highlight the importance of incorporating nutrient gradients into cultivation strategies to improve ecological interpretation and facilitate the recovery of oligotrophy-associated microorganisms from desert soils.