By Jay Skurski
1. Don’t give up on the run. It’s easy to want to bail on rushing the ball against San Francisco. The league’s fifth-ranked rushing defense is allowing 79.5 yards per game. That’s actually a slight increase from the 77.2 they allowed in leading the NFL last season. Inside linebackers NaVorro Bowman and Patrick Willis are the best tandem in the league. In the 49ers’ lone defeat this season, however, the Minnesota Vikings stayed committed to rushing the ball, with 41 attempts that produced 146 yards. The Vikings weren’t breaking off big chunks of yardage but the ground game helped produce three touchdown drives of 10-or-more plays. The strength of Buffalo’s offense is its running game with Fred Jackson and C.J. Spiller. Coach Chan Gailey has to stay committed to using it.

2. Find a way to throw at Donte.
You remember what Donte Whitner looked like in coverage, right? Well, chances are so does Gailey. Through four games, opposing quarterbacks have thrown at Whitner 11 times, according to Pro Football Focus, completing eight of those passes, but for just 42 yards. Still, he’s given up two touchdowns through the air this season, so coverage remains his weakness. The Bills need to get in situations where they have Whitner defending tight end Scott Chandler, who has an eight-inch height advantage, and with four touchdown grabs is one of the team’s best red-zone threats.

3. Put Alex Smith’s arm to the test.
San Francisco quarterback Alex Smith, right, has looked more comfortable in his second year in coach Jim Harbaugh’s system. He’s making good decisions and getting the ball out quickly. But he’s not much of a big-play threat, having thrown only four passes that have gone more than 20 yards through the air the first four games. His longest completion is just 29 yards. Buffalo’s cornerbacks need to be aggressive at the line of scrimmage to try and disrupt the receivers’ timing on those short routes Smith favors.

4. Wrap up!
The Bills missed between 10-15 tackles last week, depending on your definition of that rather subjective stat. Whatever the final number was, it was way too high. The 49ers will be sure to challenge the Bills in the run game today. San Francisco is averaging 167 yards per game, third most in the NFL, and can pound the ball with Frank Gore and Brandon Jacobs, who’s expected to make his season debut today. “Their guys are going to come off and try to knock you off the ball and out-physical you and give it to the guy downhill and let him get his yards,” Bills defensive tackle Kyle Williams said. “They have a lot of different running plays that you have to be prepared for.”

5. Answer their coach’s call.
“I think that when you come off of a loss, you have to travel all the way across the country and you have to go against a good football team you are going to be challenged mentally,” Gailey said this week. “Your toughness mentally and physically is going to be challenged. That is what we have to get ready for – and we know that.” A win today would be the upset of the week in the NFL.

Outlook: This one could get ugly. The 49ers are a physical, well-coached football team with a defense that screams Super Bowl contender. Based on the second half last week, it’s hard to believe the Bills are anything other than, well, the Bills. Prediction: 49ers 40, Bills 10