Page 85 - ITPS-8-3
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INNOSC Theranostics and
            Pharmacological Sciences                                           Activity of green-synthesized nanoparticles



            involved  in  electron  transfer  and  energy  production,    KQ76_RS08360,  fmtA,  KQ76_RS01520,  KQ76_RS13020,
                                                         40
            whereas the ferric enterobactin receptor is an outer   hssR,  ylqF,  dltB,  KQ76_RS11280/KQ76_RS11285,  KQ76_
            membrane protein responsible for transporting iron into   RS01815,  smpB,  KQ76_RS07375,  purS,  mnmG,  KQ76_
            the periplasm. 42-45  Mutations affecting iron transport   RS12955, and KQ76_RS10985.
            systems can lead to antimicrobial resistance by impairing   Describing the function of these genes is crucial
            iron uptake. This is significant because many antibiotics   for understanding how  K. pneumoniae adapts to its
            rely on iron transport pathways to enter bacterial cells.    environment, particularly in relation to antibiotic resistance,
                                                         46
            Consequently, limiting iron acquisition can enhance   pathogenicity, and microbial evolution. Mutations in these
            bacterial resistance to antimicrobial agents.      genes can significantly alter bacterial traits by affecting key
              The nutrient broth medium provides a rich source of   cellular processes such as metabolism, virulence factor
            readily available nutrients – such as carbohydrates, protein,   expression, and drug susceptibility.
            vitamins, and minerals – that enable  K. pneumoniae to   The  following  are the  functions of the  mutated  genes
            efficiently access nutrients necessary for rapid growth and   identified in K. pneumoniae control cells:
            proliferation.  In the control group, mutations are detected   (i)     sfaA/sfaD is involved in the transport of iron from
                      25
            in K. pneumoniae cells grown in this nutrient-rich medium.   the environment into the cell, supporting essential
            These mutations appear to confer advantageous traits that   cellular processes. 47
            enhance nutrient utilization, allowing the control cells to   (ii)     KQ76_RS08360 enables the recycling of adenine, a
            outcompete the treated cells and display increased growth.  critical building block of DNA. 48
              Several notable mutations are observed in the control   (iii)    fmtA is involved in cell division and bacterial cell wall
            cells, particularly in genes related to iron metabolism,   synthesis. 49
            biosynthesis, metabolism,  cell growth, detoxification,   (iv)     KQ76_RS13020 belongs to a large enzyme superfamily
            cell wall integrity, structural stability, defense, and stress   with diverse catalytic functions,  including roles in
                                                                                             50
            responses. These mutations likely provide a competitive   cell growth, metabolism, and detoxification.
            advantage in the nutrient-rich media. This also raises   (v)     hssR regulates  gene  expression  related  to iron
            concerns about stress-induced mutagenesis, as the observed   metabolism and other cellular activities. 51
            mutations  in  the  control group may  reflect an  elevated   (vi)    ylqF assists in the assembly and regulation of
            rate of adaptive mutation – potentially contributing   ribosomes. GTPases also regulate cellular functions. 52
            to future resistance development in  K. pneumoniae.   (vii)    dltB maintains cell wall integrity and regulates cation
            Nevertheless, the study demonstrates that biosynthesized   balance, contributing to resistance against cationic
            silver nanoparticles effectively inhibit bacterial growth,   antimicrobial peptides. 53
            suggesting  a  cytotoxic  effect  of  silver  nanoparticles  that   (viii)    KQ76_RS11280/KQ76_RS11285 facilitates bacterial
            interferes with essential cellular processes and disrupts   competition for resources or consumption of other
            normal cell function.                                  bacteria. 54
                                                               (ix)    KQ76_RS01815 promotes bacterial survival under
              Mutations can arise spontaneously without exposure
            to external stressors and are a key driver of bacterial   environmental stresses and induces virulence factor
                                                                   expression.
                                                                            55
            evolution. In untreated bacterial cells, mutations may result   (x)     smpB is involved in tagging and degrading proteins
            from natural genetic alterations during DNA replication.   produced from defective mRNAs and plays a role in
            While many of these changes are neutral, some may      nutrient acquisition. 56
            confer advantageous traits – such as increased antibiotic   (xi)    KQ76_RS07375   triggers  bacterial  defense
            resistance – that enhance bacterial survival in challenging   mechanisms. 57
            environments, including exposure to antimicrobials. 12
                                                               (xii)   purS is involved in the purine biosynthetic pathway. 58
              These findings highlight a critical concern: the   (xiii)    mnmG is crucial for accurate codon-anticodon
            presence  of  resistance  genes  may render nanoparticles   pairing during protein translation. 59
            ineffective. Such genes can reduce nanoparticle efficacy   (xiv)   KQ76_RS12955 is a key enzyme in glycolysis. 60
            through several mechanisms, including actively expelling   Mutations identified in E. coli-treated cells involve genes
            nanoparticles, modifying the cell membrane to prevent   associated with transport, cell division, biosynthetic
            nanoparticle entry, and chemically altering nanoparticles   adaptation, and invasion:
            to reduce their toxicity.
                                                               (i)    L-lysine  exporter  LysO/aquaporin Z (lysO/aqpZ)
              Genomic analysis reveals several mutations in the    mediates the export of L-lysine and confers resistance
            genes of control K. pneumoniae cells, including sfaA/sfaD,   to the toxic antimetabolite L-thialysine. 61


            Volume 8 Issue 3 (2025)                         79                          doi: 10.36922/ITPS025080007
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