## 1 Introduction
### Membrane Proteins of Gram-Negative Bacterium Species  
Gram-negative bacteria species are well-known and responsible for causing significant harm to mankind, making them one of the most notorious threats [28]. These bugs have an intricate cell cover with an outer membrane that acts as a molecular screen, forming an able selective permeation impediment. Like other biological membranes, this outer membrane, \"see in Figure 1\", is mainly made of a bilayer of lipids, making it impermeable to hydrophilic molecules [7; 15; 21; 24; 29; 30]. Certain water-filled membrane proteins primarily regulate the adequate inflow of these molecules. \"see Table 1 for different membrane proteins studied across different research experimental studies and Table 2 for different membrane proteins classifications\". These membrane proteins are found in various structures with different substrate specificities, regulations, and expressions [6; 21; 30]. They mostly form hollow beta-barrel structures with a hydrophobic outer surface [31]. The barrel structure makes a transmembrane pore that permits the passive flux of hydrophilic substances and acts as a functional diffusional block for nonpolar molecules/solutes [6; 7]. These proteins also exhibit particular ion-selectivity for either cations or anions [32; 33; 34]. Bacteria can alter/modify these proteins  
Figure 1: Several systems pertaining to antibiotic/ antimicrobial resistance that Gram-negative bacteria may be utilized as an overview (structural interpretation) and antibiotic/ antimicrobial resistance mechanism correlated with outer membrane proteins modification. 1. Solute transport via outer membrane proteins, 2. Loss of functional outer membrane proteins, 3. Modification of outer membrane proteins, 4. Expression of constricted outer membrane proteins, 5. Partitioning of hydrophobic molecules via the outer layer. to lower or inhibit influx through membrane channels, which, further along with efflux machinery systems, contributes towards antibiotic resistance [6; 7; 24; 31; 35]. An exhilarating task for drug design strategy is understanding membrane permeability at the molecular level to understand membrane transport's starring role in bacterial resistance processes [15]. Antibiotics, such as penicillin, carbapenems, cephalosporins, fluoroquinolones, etc., enter Gram-negative bacteria mainly through membrane channels [29; 36; 37; 38; 39]. Every slight alteration by the bacteria of these membrane proteins can considerably affect antibiotic drug therapy [24]. Many clinically significant bacterial species have been sequenced to determine the key membrane channels in the Gram-negative bacterial outer membrane [6; 7]. This reduced permeability might result from fewer membrane channels in the outer membrane and their distinct physical and chemical properties [17; 24]. These channels have different structures and specificities but have been reported to form a diffusional barrier for nonpolar solutes and antibiotic molecules [7; 15; 24; 29]. Bacteria can adapt and reduce influx through these membrane channels, leading to antibiotic resistance [7; 15; 24; 29]. Thus, the study of membrane permeability is crucial in realizing the role of membrane transport in antibiotic resistance mechanisms. Research has shown that small polar molecules roughly below 600 Dalton have the highest activity critical towards Gram-negative bacteria, suggesting that porins may be the primary entry path [15; 24; 29; 37; 40]. However, low antibiotic permeability via the outer membrane requires high doses of antibiotics, which can result in toxic side effects. Antibiotic uptake and antibiotic efficacy are complex phenomena that are influenced by various factors in bacteria [7; 15; 24; 29; 41; 42]. While the outer membrane barrier of Gram-negative bacteria is a significant obstacle to the entry of antibiotics, small hydrophilic solutes are then facilitated through the porin or outer membrane protein pathways [6; 15; 17; 24; 29; 35; 43; 44]. See Figure 1 for an overview.