Natural products, including secondary metabolites produced by plants and microorganisms, have long been studied for their antimicrobial activity in the search for eco-friendly substitutes for synthesized chemicals [
118]. Di(2-ethylhexyl) phthalate and di-
n-butyl phthalate isolated from
B. mcbrellneri show broad-spectrum antibacterial activity [
108]. Di(2-ethylhexyl) phthalate can inhibit the growth of gram-positive (
S. epidermidis, MIC of 9.37 µg/mL;
S. aureus, MIC of 18.75 µg/mL) and gram-negative bacteria (
E. coli, MIC of 37.5 µg/mL;
P. aeruginosa and
Klebsiella pneumoniae, MIC at 75 µg/mL for both). Di-
n-butyl phthalate also inhibits the growth of gram-positive (
Bacillus subtilis and
S. epidermidis, MIC at 18.75 µg/mL for both) as well as gram-negative bacteria (
E. coli and
P. aeroginosa, MIC at 37.5 µg/mL for both). Di(2-ethylhexyl) phthalate isolated from the flowers of
Calotropis gigantean exerts antimicrobial activity against
B. subtilis with a MIC of 32 µg/mL [
119]. There are also reports on the antimicrobial activity of di-
n-butyl phthalate isolated from
Streptomyces albidoflavus showing a MIC for
E. coli of 53 µg/mL, with
B. subtilis at 84 µg/mL [
112]. Four phthalate derivatives isolated from
E. crassipes also exert significant antibacterial activity against gram-positive bacteria (
B. subtilis and
Streptococcus faecalis) and gram-negative bacteria
E. coli, and antifungal activity against
Candida albicans [
95]. In another study, El-Mehalawy et al. (2008) [
120] found that di(2-ethylhexyl) phthalate could be produced by certain bacteria, including
Tsukamurella inchonensis, Corynebacterium nitrilophilus, and
Cellulosimicrbium cellulans, and di(2-ethylhexyl) phthalate has the function to inhibit fungal spore germination, cell membrane growth, and the production of total lipids and total protein. Li et al. (2021) [
121] isolated di-
n-butyl phthalate from a new marine
Streptomyces sp. and found this compound significantly inhibited spore germination and mycelial growth of
Colletotrichum fragariae. In addition to this, an obvious decrease was detected in sugar and protein contents of
C. fragariae mycelia. Other studies have shown similar results. For instance, di-
n-butyl phthalate was reported to inhibit spore germination and mycelium growth of
Colletotrichum gloeosporioides,
Colletotrichum musae, and
Gaeumannomyces graminis [
122,
123,
124].
Janu and Jayanthy (2014) found that diethyl phthalate derived from the fungus
Aspergillus sp. increased the superoxide production and exerted ROS generated oxidative stress in the cytoplasm of bacterial cells, which eventually led to cell death [
125]. In addition, diethyl phthalate with antimicrobial properties was reported for its ability to interfere with quorum sensing mediated virulence factors and biofilm formation in
Pseudomonas aeruginosa [
126,
127]. Another study demonstrated that dimethyl phthalate (concentration ranged from 20 to 40 mg/L) greatly inhibited the growth and glucose utilization of
Pseudomonas fluorescens, meanwhile the surface hydrophobicity and membrane permeability of
P. fluorescens were also increased. Dimethyl phthalate could lead to deformation of the cell membrane and misopening of membrane channels. Additionally, RNA-Seq and RT-qPCR results revealed that the expression of some genes in
P. fluorescens were altered, including the genes involved in energy metabolism, ATP-binding cassette transporting, and two-component systems by dimethyl phthalate [
128].